|
1
|
Mousa LN, Jarrar Y, Gharaibeh M, Alhawari H. Effects of tumor necrosis factor- α rs1800629 and interleukin- 10 rs1800872 genetic variants on type 2 diabetes mellitus susceptibility and metabolic parameters among Jordanians. Drug Metab Pers Ther 2024; 39:81-87. [PMID: 38741519 DOI: 10.1515/dmpt-2024-0002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/01/2024] [Indexed: 05/16/2024]
Abstract
OBJECTIVES Diabetes mellitus (DM) is a complex chronic illness with diverse pathogenesis and associations with health complications. Genetic factors significantly contribute to DM development, and tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) genes play major roles. This study aims to explore the influence of TNF-α rs1800629 and IL-10 rs1800872 genetic variants on T2DM development in Jordanian patients at Jordan University Hospital. METHODS One-hundred and 60 diabetic and 159 non-diabetic subjects were genotyped for TNF-α rs1800629. Additionally, 181 diabetic and 191 non-diabetic subjects were genotyped for IL-10 rs1800872 using PCR-RFLP genotyping method. The demographic, lipid, and glycemic parameters of the patients were obtained from the computer records in the hospital. RESULTS TNF-α rs1800629 and IL-10 rs1800872 genetic variants exhibited significant different frequencies in non-T2DM subjects and T2DM patients. The difference in TNF-α rs1800629 genotype frequency between non-T2DM and T2DM participants was significant under the dominant model, while the IL-10 rs1800872 genotype frequency was significant under the recessive model. A significant association (p<0.05) was observed between TNF-α rs1800629 and total cholesterol levels, and between IL-10 rs1800872 polymorphism and glycosylated hemoglobin (HbA1c) and creatinine levels among T2DM patients. CONCLUSIONS TNF-α rs1800629 and IL-10 rs1800872 are identified as genetic risk factors for T2DM. These variants also correlate with variations in cholesterol, HbA1c, and creatinine levels among T2DM patients. Larger clinical studies are warranted to validate these findings.
Collapse
Affiliation(s)
- Lana Nasrallah Mousa
- Department of Pharmacology, Faculty of Medicine, 54658 The University of Jordan , Amman, Jordan
| | - Yazun Jarrar
- Department of Basic Medical Sciences, Faculty of Medicine, Al-Balqa Applied University, Al-Salt, Jordan
| | - Munir Gharaibeh
- Department of Pharmacology, Faculty of Medicine, 54658 The University of Jordan , Amman, Jordan
| | - Hussam Alhawari
- Department of Internal Medicine, School of Medicine, The University of Jordan, Amman, Jordan
| |
Collapse
|
|
2
|
Urcar Gelen S, Ozkanlar S, Gedikli S, Atasever M. The investigation of the effects of monosodium glutamate on healthy rats and rats with STZ-induced diabetes. J Biochem Mol Toxicol 2024; 38:e23612. [PMID: 38084638 DOI: 10.1002/jbt.23612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 06/14/2023] [Accepted: 11/21/2023] [Indexed: 01/18/2024]
Abstract
Monosodium glutamate (MSG, E621) is a flavor-enhancing food additive used widely in the food preparation industry and consumed regularly. It is considered that long-term consumption of MSG causes metabolic syndrome and obesity. Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood sugar, polyuria, polydipsia, and polyphagia, in which insulin secreted from pancreatic β cells is inadequate for maintaining blood glucose homeostasis. Rats were application 65 mg/kg streptozotocin (STZ) solution intraperitoneally and a diabetes model was created. For this purpose, freshly prepared STZ was injected into the peritoneum. Tumor necrosis factor-α, interleukin (IL)-10, IL-6, and IL-1β levels in STZ, MSG, and STZ + MSG groups were found to be significantly increased in inflammation parameters measured on the 28th day of administration when compared to the Control Group (p < 0.001). Also, although malondialdehyde (MDA) levels increased significantly in the STZ + MSG group when compared to the control group (p < 0.001), glutathione (GSH), and superoxide dismutase (SOD) levels were significantly decreased in the STZ, MSG, and STZ + MSG groups when compared to the control group (p < 0.001). Also, although glucose levels increased significantly in STZ and STZ + MSG at the end of the 28th day (p < 0.01), insulin levels decreased in STZ, MSG, and STZ + MSG groups when compared to the control groups (p < 0.01). As a result, it was found that STZ and MSG application significantly increased cytokine production, increased MDA, which is an oxidant parameter in pancreatic tissue, and decreased antioxidants (GSH and SOD) when compared to the control groups. It was also found that MSG disrupted the normal histological structure in pancreatic cells, and the damage was much more in both exocrine and endocrine pancreatic areas in the STZ + MSG group when compared to the STZ and MSG groups. It was considered that with the increased use of MSG, the susceptibility to DM might increase along with tissue damage significantly in diabetic groups, therefore, MSG must be used in a limited and controlled manner.
Collapse
Affiliation(s)
- Sevda Urcar Gelen
- Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Seckin Ozkanlar
- Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Semin Gedikli
- Department of Histology and Embryology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| | - Mustafa Atasever
- Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey
| |
Collapse
|
|
3
|
Xie W, Zhang L, Wang J, Wang Y. Association of HHEX and SLC30A8 Gene Polymorphisms with Gestational Diabetes Mellitus Susceptibility: A Meta-analysis. Biochem Genet 2023; 61:2203-2221. [PMID: 37103601 DOI: 10.1007/s10528-023-10385-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2022] [Accepted: 04/14/2023] [Indexed: 04/28/2023]
Abstract
Genetics plays a role in the development of gestational diabetes mellitus (GDM), which poses serious risks to pregnant women and their children. Several studies have demonstrated a link between GDM susceptibility and rs13266634 C/T polymorphism in SLC30A8 gene and rs1111875 C/T and rs5015480 C/T, which are located near the linkage disequilibrium block containing the IDE, HHEX, and KIF11 genes. However, the results are conflicting. Therefore, we aimed to investigate the association between susceptibility to GDM and HHEX and SLC30A8 gene polymorphisms. PubMed, Web of Science, EBSCO, CNKI, Wanfang Data, VIP, and SCOPUS were used to search for research articles. The quality of the selected literature was evaluated using the Newcastle-Ottawa scale. A meta-analysis was performed using Stata 15.1. Allelic, dominant, recessive, homozygote, and heterozygote models were used for the analysis. Nine articles with 15 studies were included. (1) Four studies about HHEX rs1111875 showed that the C allele was associated with the susceptibility to GDM; (2) three studies on HHEX rs5015480 indicated that the C allele in rs5015480 was significantly associated with GDM; (3) eight studies about SLC30A8 rs13266634 showed that the C allele was significantly associated with the susceptibility to GDM; and (4) a subgroup analysis showed that the rs5015480 polymorphism in HHEX and rs13266634 polymorphism in SLC30A8 gene were associated with GDM susceptibility in Asians. The meta-analysis provided evidence that the C allele in rs1111875 and rs5015480 in HHEX and rs13266634 in SLC30A8 can increase the risk of GDM.PROSPERO registration number CRD42022342280.
Collapse
Affiliation(s)
- Wanting Xie
- Department of Physical Fitness and Health, School of Sport Science, Beijing Sport University, No.48, Xinxi Road, Haidian District, Beijing, 100084, China
| | - Liuwei Zhang
- Department of Physical Fitness and Health, School of Sport Science, Beijing Sport University, No.48, Xinxi Road, Haidian District, Beijing, 100084, China.
- Key Laboratory of Exercise and Physical Fitness, Ministry of Education, Beijing Sport University, Beijing, 100084, China.
| | - Jiawei Wang
- Department of Physical Fitness and Health, School of Sport Science, Beijing Sport University, No.48, Xinxi Road, Haidian District, Beijing, 100084, China
| | - Yirui Wang
- Department of Physical Fitness and Health, School of Sport Science, Beijing Sport University, No.48, Xinxi Road, Haidian District, Beijing, 100084, China
| |
Collapse
|
|
4
|
Uryash A, Umlas J, Mijares A, Adams JA, Lopez JR. Enhancing Muscle Intracellular Ca 2+ Homeostasis and Glucose Uptake: Passive Pulsatile Shear Stress Treatment in Type 2 Diabetes. Biomedicines 2023; 11:2596. [PMID: 37892970 PMCID: PMC10604129 DOI: 10.3390/biomedicines11102596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/19/2023] [Accepted: 09/19/2023] [Indexed: 10/29/2023] Open
Abstract
Type 2 diabetes mellitus (T2D) is a significant global public health problem that has seen a substantial increase in the number of affected individuals in recent decades. In a murine model of T2D (db/db), we found several abnormalities, including aberrant intracellular calcium concentration ([Ca2+]i), decreased glucose transport, increased production of reactive oxygen species (ROS), elevated levels of pro-inflammatory interleukins and creatine phosphokinase (CK), and muscle weakness. Previously, we demonstrated that passive pulsatile shear stress, generated by sinusoidal (headward-forward) motion, using a motion platform that provides periodic acceleration of the whole body in the Z plane (pGz), induces the synthesis of nitric oxide (NO) mediated by constitutive nitric oxide synthase (eNOS and nNOS). We investigated the effect of pGz on db/db a rodent model of T2D. The treatment of db/db mice with pGz resulted in several beneficial effects. It reduced [Ca2+]i overload; enhanced muscle glucose transport; and decreased ROS levels, interleukins, and CK. Furthermore, pGz treatment increased the expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), and neuronal nitric oxide synthase (nNOS); reduced inducible nitric oxide synthase (iNOS); and improved muscle strength. The cytoprotective effects of pGz appear to be mediated by NO, since pretreatment with L-NAME, a nonspecific NOS inhibitor, abolished the effects of pGz on [Ca2+]i and ROS production. Our findings suggest that a non-pharmacological strategy such as pGz has therapeutic potential as an adjunct treatment to T2D.
Collapse
Affiliation(s)
- Arkady Uryash
- Division of Neonatology, Mount Sinai Medical Center, Miami, FL 33140, USA; (A.U.); (J.A.A.)
| | - Jordan Umlas
- Division of Neonatology, Mount Sinai Medical Center, Miami, FL 33140, USA; (A.U.); (J.A.A.)
| | - Alfredo Mijares
- Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas, Caracas 21827, Venezuela;
| | - Jose A. Adams
- Division of Neonatology, Mount Sinai Medical Center, Miami, FL 33140, USA; (A.U.); (J.A.A.)
| | - Jose R. Lopez
- Department of Research, Mount Sinai Medical Center, Miami Beach, FL 33140, USA
| |
Collapse
|
|
5
|
Ademola SA, Bamikole OJ, Amodu OK. Is TNF alpha a mediator in the co-existence of malaria and type 2 diabetes in a malaria endemic population? Front Immunol 2023; 14:1028303. [PMID: 37215099 PMCID: PMC10196125 DOI: 10.3389/fimmu.2023.1028303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 04/25/2023] [Indexed: 05/24/2023] Open
Abstract
Malaria remains a disease of public health importance globally, especially in sub-Saharan Africa. Malaria deaths reduced globally steadily between 2000-2019, however there was a 10% increase in 2020 due to disruptions in medical service during the COVID-19 pandemic. Globally, about 96% of malaria deaths occurred in 29 countries; out of which, four countries (Nigeria, the Democratic Republic of the Congo, the Niger, and the United Republic of Tanzania) accounted for just over half of the malaria deaths. Nigeria leads the four countries with the highest malaria deaths (accounting for 31% globally). Parallelly, sub-Saharan Africa is faced with a rise in the incidence of Type 2 diabetes (T2D). Until recently, T2D was a disease of adulthood and old age. However, this is changing as T2D in children and adolescents is becoming an increasingly important public health problem. Nigeria has been reported to have the highest burden of diabetes in Africa with a prevalence of 5.77% in the country. Several studies conducted in the last decade investigating the interaction between malaria and T2D in developing countries have led to the emergence of the intra-uterine hypothesis. The hypothesis has arisen as a possible explanation for the rise of T2D in malaria endemic areas; malaria in pregnancy could lead to intra-uterine stress which could contribute to low birth weight and may be a potential cause of T2D later in life. Hence, previous, and continuous exposure to malaria infection leads to a higher risk of T2D. Current and emerging evidence suggests that an inflammation-mediated link exists between malaria and eventual T2D emergence. The inflammatory process thus, is an important link for the co-existence of malaria and T2D because these two diseases are inflammatory-related. A key feature of T2D is systemic inflammation, characterized by the upregulation of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) which leads to impaired insulin signaling. Malaria infection is an inflammatory disease in which TNF-α also plays a major role. TNF-α plays an important role in the pathogenesis and development of malaria and T2D. We therefore hypothesize that TNF-α is an important link in the increasing co-existence of T2D.
Collapse
|
|
6
|
Sharbatdar Y, Mousavian R, Noorbakhsh Varnosfaderani SM, Aziziyan F, Liaghat M, Baziyar P, Yousefi Rad A, Tavakol C, Moeini AM, Nabi-Afjadi M, Zalpoor H, Kazemi-Lomedasht F. Diabetes as one of the long-term COVID-19 complications: from the potential reason of more diabetic patients' susceptibility to COVID-19 to the possible caution of future global diabetes tsunami. Inflammopharmacology 2023; 31:1029-1052. [PMID: 37079169 PMCID: PMC10116486 DOI: 10.1007/s10787-023-01215-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Accepted: 03/27/2023] [Indexed: 04/21/2023]
Abstract
According to recent researches, people with diabetes mellitus (type 1 and 2) have a higher incidence of coronavirus disease 2019 (COVID-19), which is caused by a SARS-CoV-2 infection. In this regard, COVID-19 may make diabetic patients more sensitive to hyperglycemia by modifying the immunological and inflammatory responses and increasing reactive oxygen species (ROS) predisposing the patients to severe COVID-19 and potentially lethal results. Actually, in addition to COVID-19, diabetic patients have been demonstrated to have abnormally high levels of inflammatory cytokines, increased virus entrance, and decreased immune response. On the other hand, during the severe stage of COVID-19, the SARS-CoV-2-infected patients have lymphopenia and inflammatory cytokine storms that cause damage to several body organs such as β cells of the pancreas which may make them as future diabetic candidates. In this line, the nuclear factor kappa B (NF-κB) pathway, which is activated by a number of mediators, plays a substantial part in cytokine storms through various pathways. In this pathway, some polymorphisms also make the individuals more competent to diabetes via infection with SARS-CoV-2. On the other hand, during hospitalization of SARS-CoV-2-infected patients, the use of some drugs may unintentionally lead to diabetes in the future via increasing inflammation and stress oxidative. Thus, in this review, we will first explain why diabetic patients are more susceptible to COVID-19. Second, we will warn about a future global diabetes tsunami via the SARS-CoV-2 as one of its long-term complications.
Collapse
Affiliation(s)
- Yasamin Sharbatdar
- Department of Anesthesiology, School of Allied Medical Sciences, Ahvaz Jundishapur, University of Medical Sciences, Ahvaz, Iran
| | - Ronak Mousavian
- Department of Clinical Biochemistry, School of Medicine, Cellular and Molecular Research Center, Medical Basic Science Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Fatemeh Aziziyan
- Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mahsa Liaghat
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Department of Medical Laboratory Sciences, Faculty of Medical Sciences, Islamic Azad University, Kazerun Branch, Kazerun, Iran
| | - Payam Baziyar
- Department of Molecular and Cell Biology, Faculty of Basic Science, University of Mazandaran, Babolsar, Iran
| | - Ali Yousefi Rad
- Department of Biochemistry, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
| | - Chanour Tavakol
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Amir Mansour Moeini
- Department of Internal Medicine, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran.
| | - Hamidreza Zalpoor
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
- Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Fatemeh Kazemi-Lomedasht
- Venom and Biotherapeutics Molecules Laboratory, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
| |
Collapse
|
|
7
|
Singh S, Shukla AK, Usman K, Banerjee M. Pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) in newly diagnosed Indian type 2 diabetes patients undergoing metformin monotherapy. Pharmacogenet Genomics 2023; 33:51-58. [PMID: 36853844 DOI: 10.1097/fpc.0000000000000493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
OBJECTIVES Type 2 diabetes (T2D) imposes an enormous burden all over the world in both developed and developing countries. Inter-individual differences are attributed to polymorphisms in candidate genes resulting in altered absorption, transportation, distribution, and metabolism of oral antidiabetic drugs (OADs). Hence, the present study was undertaken to evaluate the pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) on metformin monotherapy in newly diagnosed untreated T2D patients. METHODS Newly diagnosed T2D patients ( n = 500) were enrolled according to inclusion/exclusion criteria. Initially, enrolled subjects were prescribed metformin monotherapy and followed up for at least 12 weeks. Response to metformin was evaluated in 478 patients who revisited for follow-up by measuring HbA1c. RESULT Out of 478 patients, 373 were responders to metformin monotherapy while 105 were non-responders. The pharmacogenetic impact was evaluated by genotype, haplotype, and pharmacogenetic analyses. 'GG' genotype and 'G' allele of SLC22A1 rs628031 G/A were observed in 48.8% and 67.7% of Met responders, respectively, while 20.9% and 49.1 % were in non-responders. Therefore, there was a 2.18-fold increase in the success rate of Met therapeutics. CONCLUSION Individuals carrying the 'GG' genotype or 'G' allele for SLC22A1 gene variant rs628031 G/A are better responders for Metformin monotherapy.
Collapse
Affiliation(s)
- Shalini Singh
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow
| | - Ashwin Kumar Shukla
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow
| | - Kauser Usman
- Department of Medicine, King George's Medical University Lucknow, India
| | - Monisha Banerjee
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow
| |
Collapse
|
|
8
|
Research Progress of Population Pharmacokinetic of Metformin. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4071111. [PMID: 36578804 PMCID: PMC9792241 DOI: 10.1155/2022/4071111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Revised: 11/21/2022] [Accepted: 12/03/2022] [Indexed: 12/23/2022]
Abstract
Metformin is commonly used as first-line treatment for T2DM (type2 diabetes mellitus). Owing to the high pharmacokinetic (PK) variability, several population pharmacokinetic (PPK) models have been developed for metformin to explore potential covariates that affect its pharmacokinetic variation. This comprehensive review summarized the published PPK studies of metformin, aimed to summarize PPK models of metformin. Most studies described metformin pharmacokinetics as a 2-compartment (2-CMT) model with 4 study describing its pharmacokinetics as 1-compartment (1-CMT). Studies on metformin PPK have shown that obesity, creatinine clearance (CLCr), gene polymorphism, degree of renal function damage, and pathological conditions all have a certain impact on the PK parameters of metformin. It is particularly important to formulate individualized dosing regimens. For future PPK studies of metformin, we believe that more attention should be paid to special populations.
Collapse
|
|
9
|
Mohammed DM, Elsayed N, Abou Baker DH, Ahmed KA, Sabry BA. Bioactivity and antidiabetic properties of Malva parviflora L. leaves extract and its nano-formulation in streptozotocin-induced diabetic rats. Heliyon 2022; 8:e12027. [PMID: 36531617 PMCID: PMC9747597 DOI: 10.1016/j.heliyon.2022.e12027] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/17/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
Diabetes is a drastic health problem resulting from an endocrine disorder. M. parviflora L. might represent an antioxidant-rich food source and thus applies to pharmaceutical and therapeutic applications in oxidative stress-related degenerative diseases. In the current work, we assessed the antidiabetic activity of M. parviflora L. leaves extract and its nano-formulation in rats. M. parviflora L. bioactivity was evaluated by both antioxidant and antimicrobial assays. The nano-formulation characteristics (Mass, TEM, and Zeta potential) were evaluated. Twenty-four male Sprague-Dawley rats were administered streptozotocin (STZ) intraperitoneally for only one dose (35 mg/kg body weight). All of the nutritional and biochemical parameters were statistically analyzed. The results showed that M. parviflora L. is rich in phenolics and flavonoids with high antioxidant action. The antifungal activity of the extract was evident, especially with Fusarium culmorum and aspergillus flavus. The extract and its nano-formulation have shown antidiabetic properties when tested on diabetic rats as they improved all the biochemical parameters; decreased glucose level in serum, increased insulin production, marked improvement in lipid profile, liver and kidney functions, and that was more proved with the histopathological examinations. Conclusively, M. parviflora L. extract and its nano-formulation could attenuate or effectively help in controlling diabetes through its therapeutic properties exhibited by the action of the plant antioxidant components.
Collapse
Affiliation(s)
- Dina Mostafa Mohammed
- Nutrition and Food Sciences Department, National Research Centre, Dokki, Cairo, 12622, Egypt
| | - Nesren Elsayed
- Food Science Department, Faculty of Agriculture, Cairo University, Giza, Egypt
| | - Doha H. Abou Baker
- Medicinal and Aromatic Plants Department, National Research Centre, Dokki, Cairo, 12622, Egypt
| | - Kawkab A. Ahmed
- Pathology Department, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Bassem A. Sabry
- Food Toxicology and Contaminants Department, National Research Centre, Dokki, Cairo, 12622, Egypt
| |
Collapse
|
|
10
|
Chikoti S, Najiya U, Sumanlatha G, Jahan P. Cytokine gene variants of TNF-α and IL-10 in the propensity of type 2 diabetes in south Indian population. J Diabetes Complications 2022; 36:108304. [PMID: 36148706 DOI: 10.1016/j.jdiacomp.2022.108304] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Revised: 07/14/2022] [Accepted: 09/02/2022] [Indexed: 10/14/2022]
Abstract
Chronic inflammation plays an important role in type 2 diabetes mellitus (T2DM), a common endocrinological pro-inflammatory disorder associated with insulin resistance. The objective of the present study is to see individual and combined effect of TNF-α (rs361525, rs1800629) and IL-10 (rs1800872, rs1800896) genes on T2DM susceptibility The genotyping was carried out in 200 T2DM patients and 200 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using suitable primers. The results shown that TNF-α (GA of rs361525 & rs1800629) and IL-10 (AA of rs1800872 & GA of rs1800896) genes are significantly linked with T2DM development. The presence of AA-GA genotype combination for both TNF-α and IL-10 genes were elevating the risk of T2DM. Moreover, individuals bearing haplotypes AAAA, AACA and AAAG experience the increased risk of T2DM. Furthermore, gene-gene interaction analysis shown that TNF-α (GA of rs361525 & rs1800896) gene redundantly confer 3.4-fold elevated risk for T2DM. In gene-environment interaction, GA of TNF-α -1800896, W/H ratio and TG/HDL ratio were redundantly interacted each other and increase the risk of T2DM by 67-times. In conclusion, our results reveal that there is a significant association between foresaid TNF-α, IL-10 gene promoter polymorphisms and T2DM development. To the best of our knowledge this study is the first of its kind in the literature reporting the epistatic association of TNF-α (rs1800629G/A) gene with TG/HDL ratio and W/H ratio over IL-10 gene polymorphisms for T2DM susceptibility among south Indians.
Collapse
Affiliation(s)
- Swetha Chikoti
- Department of Genetics, Osmania University, Hyderabad, India
| | - Umme Najiya
- Department of Genetics, Osmania University, Hyderabad, India
| | | | - Parveen Jahan
- School of Sciences, Maulana Azad National Urdu University, Hyderabad, India.
| |
Collapse
|
|
11
|
Yalçın T, Oğuz SH, Bayraktar M, Rakıcıoğlu N. Anthropometric measurements and serum TNF-α, IL-6 and adiponectin in type 2 diabetes. Diabetol Int 2022; 13:396-406. [PMID: 35463864 PMCID: PMC8980124 DOI: 10.1007/s13340-021-00553-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 10/14/2021] [Indexed: 01/22/2023]
Abstract
Objective To investigate the effect of anthropometric measurements on serum adiponectin and inflammatory markers in Type 2 diabetes mellitus (T2DM). Methods This study was conducted with 46 subjects newly diagnosed with T2DM and 30 healthy volunteers free from pre-existing inflammatory disease, cancer, Type 1 diabetes and using any medications. Demographic, clinical and anthropometric data were collected. The anthropometric measurements and insulin resistance components (fasting plasma glucose (FPG), HbA1c, fasting insulin, HOMA-IR) were analyzed. HOMA-β values were calculated to measure pancreatic beta cell functions. Serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were measured to determine the presence of inflammation and serum adiponectin levels were assessed. Results Individuals with T2DM showed higher body mass index (BMI), body fat percentage, waist circumference (WC), waist-to-hip ratio and waist-to-height ratio values. Serum cytokine levels were higher but adiponectin levels were lower in diabetic patients. Serum concentrations of CRP were found to be significantly correlated with WC and body fat mass (kg and %); TNF-α was significantly associated with WC and waist-to-hip ratio in individuals with T2DM. Adiponectin was negatively correlated with WC and waist-to-hip ratio in healthy subjects. Conclusions Prevention of obesity and central adiposity is an important factor to prevent elevations in inflammatory cytokine levels in diabetic patients.
Collapse
Affiliation(s)
- Tuba Yalçın
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Izmir Katip Çelebi University, 35620 İzmir, Turkey
| | - Seda Hanife Oğuz
- Department of Endocrinology, Division of Endocrinology and Metabolism, Hacettepe University, 06100 Ankara, Turkey
| | - Miyase Bayraktar
- Department of Endocrinology, Division of Endocrinology and Metabolism, Hacettepe University, 06100 Ankara, Turkey
| | - Neslişah Rakıcıoğlu
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hacettepe University, 06100 Ankara, Turkey
| |
Collapse
|
|
12
|
Cai H, Jin S, Lin J, Yu L, Qian P, Chen W. IL-34 was high in serum of women with polycystic ovary syndrome and may function as potential diagnostic biomarker and therapeutic target. J Obstet Gynaecol Res 2022; 48:973-979. [PMID: 35199410 DOI: 10.1111/jog.15141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 11/23/2021] [Accepted: 12/18/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in females of reproductive age, with a prevalence of 20%-33% in the general population. Interleukin (IL)-34 is a recently explored proinflammatory cytokine and is an important modulator in different disease types. However, the function of IL-34 in PCOS has yet to be investigated. OBJECTIVE The purpose of this study was to determine the IL-34 serum level in women with PCOS and to compare it to that of a relatively healthy control group. Focusing on its relationship with IL-6, TNF-α, and IL-1β and homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and low-density lipoprotein cholesterol (LDL-C). MATERIALS AND METHODS In this study, blood samples were obtained from 100 women with PCOS and 100 healthy control women for the purpose of estimating their serum levels of IL-34, IL-6, TNF-α, and IL-1β using the enzyme-linked immunosorbent assay technique. RESULTS Serum levels of IL-34, IL-6, TNF-α, and IL-1β were all higher in PCOS women than in healthy controls, and the difference was highly statistically significant. Serum IL-34 concentration was positively correlated with IL-6, TNF-α, and IL-1β concentration. Additionally, serum concentrations of IL-34 were positively correlated with HOMA-IR, triglyceride, and LDL-C. CONCLUSION When compared to normal women, IL-34, IL-6, TNF-α, and IL-1β levels were highly statistically significant in PCOS, and these high levels were associated with other cytokines (IL-6, TNF-α, and IL-1β), HOMA-IR, triglyceride, and LDL-C.
Collapse
Affiliation(s)
- Huaping Cai
- Department of Gynaecology, Tongxiang Maternal and Child Health Hospital, Jiaxing, China
| | - Shuman Jin
- Department of Clinical Laboratory, Tongxiang Maternal and Child Health Hospital, Jiaxing, China
| | - Jinfang Lin
- Department of Gynaecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Liying Yu
- Department of Gynaecology, Tongxiang Maternal and Child Health Hospital, Jiaxing, China
| | - Panlian Qian
- Department of Gynaecology, Tongxiang Maternal and Child Health Hospital, Jiaxing, China
| | - Weimin Chen
- Department of Gynaecology, Tongxiang Maternal and Child Health Hospital, Jiaxing, China
| |
Collapse
|
|
13
|
Dos Santos Haber JF, Chagas EFB, Barbalho SM, Sgarbi JA, Haber RSDA, de Labio RW, Payão SLM. Level of physical activity and gene expression of IL-10 and TNF-α in children and adolescents with Type 1 diabetes. J Diabetes Complications 2022; 36:108104. [PMID: 34924277 DOI: 10.1016/j.jdiacomp.2021.108104] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 11/03/2021] [Accepted: 12/05/2021] [Indexed: 12/22/2022]
Abstract
AIMS The gene expressions of IL-10 and TNF-α have been identified as important factors of the clinical condition in type I diabetes mellitus (DM1). However, the effect of physical exercise on the expression of these markers is poorly understood. Our objective was to evaluate the relationship between the level of physical activity (LPA) and the gene expressions of IL-10 and TNF-α, as the relationship with glycemic control and insulin reserve in children and adolescents with DM1. METHODS 108 participants (1-23 years), were divided into 4 groups: DM1 with ketoacidosis (KETO) (n = 15); Decompensated DM1 (DM1d) (n = 32); Compensated DM1 (DM1c) (n = 30); and healthy control (C) (n = 30). The level of physical activity (LPA) was classified as low active, active, and very active. So evaluated Fasting blood glucose, HbA1c, C-peptide, and gene expressions of IL-10 and TNF-α. RESULTS The increase in the level of physical activity significantly affected the expression of TNF-α in the DMd and C groups. The increase in LPA from low to active reduced the gene expression of IL-10; however, the increase in NAF from active to very active was associated with an increase in IL-10 gene expression. A very active LPA contributes to reducing HbA1c and an increase in C-peptide in the KETO group. CONCLUSION The increase in LPA demonstrated a significant effect on the improvement of IL-10 and TNF-α gene expression in the KETO and DMd groups; however, in the KETO group, improvements were also observed in the percentage of HbA1C and C-peptide.
Collapse
Affiliation(s)
- Jesselina Francisco Dos Santos Haber
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília, São Paulo, Brazil; Interdisciplinary Center on Diabetes (CENID) - UNIMAR, Marília, SP, Brazil
| | - Eduardo Federighi Baisi Chagas
- Interdisciplinary Center on Diabetes (CENID) - UNIMAR, Marília, SP, Brazil; Postgraduate Program in Structural and Functional Interactions in Rehabilitation - UNIMAR, Marília, SP, Brazil; Postgraduate of Health and Aging Program, Faculdade de Medicina de Marilia, Marília, São Paulo, Brazil
| | - Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília, São Paulo, Brazil; Interdisciplinary Center on Diabetes (CENID) - UNIMAR, Marília, SP, Brazil; Postgraduate Program in Structural and Functional Interactions in Rehabilitation - UNIMAR, Marília, SP, Brazil.
| | - Jose Augusto Sgarbi
- Postgraduate of Health and Aging Program, Faculdade de Medicina de Marilia, Marília, São Paulo, Brazil
| | - Rafael Santos De Argollo Haber
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho, 1001, Marília, São Paulo, Brazil
| | - Roger William de Labio
- Postgraduate of Health and Aging Program, Faculdade de Medicina de Marilia, Marília, São Paulo, Brazil
| | - Spencer Luiz Marques Payão
- Postgraduate of Health and Aging Program, Faculdade de Medicina de Marilia, Marília, São Paulo, Brazil; Department of Genetics - Faculdade de Medicina de Marília, Marília, São Paulo, Brazil
| |
Collapse
|
|
14
|
Mohammad A, Falahi E, Mohd Yusof BN, Hanipah ZN, Sabran MR, Mohamad Yusof L, Gheitasvand M. The effects of the ginger supplements on inflammatory parameters in type 2 diabetes patients: A systematic review and meta-analysis of randomised controlled trials. Clin Nutr ESPEN 2021; 46:66-72. [PMID: 34857250 DOI: 10.1016/j.clnesp.2021.10.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 09/28/2021] [Accepted: 10/17/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVES The effect of ginger supplements on inflammatory biomarkers and oxidative stress in patients with type 2 diabetes (T2DM) has been investigated, but findings are inconsistent. This systematic review and meta-analysis were conducted to determine the effects of ginger supplementation on inflammatory parameters (high-sensitivity C-reactive protein [hs-CRP], tumour necrosis factor-alpha [TNF-α], and interleukin-6 [IL-6]) in patients with T2DM. METHODS We performed a systematic search using PubMed, Scopus, Cochrane Library, Web of Science for randomised controlled trials (RCTs), published until March 17, 2021. The quality assessment was carried out using the Cochrane Collaboration risk of bias tool. The Q-test and I 2 tests were used for the determination of heterogeneity of the included studies. Data were pooled using a random-effects model, and weighted mean difference (WMD) was used for the overall effect size. RESULTS Pooled findings of the five RCTs demonstrated that ginger supplementations had significantly reduced hs-CRP (WMD -0.42 mg/L; 95% CI, -0.78, -0.05, P = 0.03), TNF-α (-2.13 pg/mL; 95% CI: -3.41, -0.86, P = 0.001), and IL-6 (WMD: -0.61 pg/mL; 95% CI: -0.92, -0.30, P = 0.001) levels in patients with T2DM. The quality assessment of the studies showed that all of the included studies were at high risk of bias. CONCLUSIONS The meta-analysis shows that ginger supplementations reduced inflammatory parameters in patients with T2DM. Nonetheless, the reduction is relatively small, and its meaningful clinical effects are unknown. Future high-quality RCTs are needed to confirm the beneficial effects of ginger supplementation in patients with T2DM.
Collapse
Affiliation(s)
- Abolfathi Mohammad
- Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia.
| | - Ebrahim Falahi
- Nutritional Health Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran.
| | - Barakatun-Nisak Mohd Yusof
- Department of Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia; Research Centre of Excellence for Nutrition and Non-communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia; Institute of Social Sciences, Universiti Putra Malaysia, Malaysia.
| | - Zubaidah Nor Hanipah
- Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia.
| | - Mohd Redzwan Sabran
- Department of Nutrition, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Malaysia.
| | - Loqman Mohamad Yusof
- Department of Companion Animal Medicine and Surgery, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Malaysia.
| | - Mohsen Gheitasvand
- Department of Pathology, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran.
| |
Collapse
|
|
15
|
Ayelign B, Negash M, Andualem H, Wondemagegn T, Kassa E, Shibabaw T, Akalu Y, Molla MD. Association of IL-10 (- 1082 A/G) and IL-6 (- 174 G/C) gene polymorphism with type 2 diabetes mellitus in Ethiopia population. BMC Endocr Disord 2021; 21:70. [PMID: 33858419 PMCID: PMC8051082 DOI: 10.1186/s12902-021-00738-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 04/07/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Interleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Therefore, this study aimed to assess IL-6 (- 174 G/C) and IL-10 (- 1082 A/G) gene polymorphism, and its association with T2DM, North West Ethiopia. METHODS A comparative cross-sectional study from January to May 2018 was conducted on study participants with T2DM and apparently healthy controls. Deoxyribonucleic acid (DNA) extraction and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction to detect polymorphism of IL-6 and IL-10 gene at the position - 174 and - 1082, respectively. The logistic regression model was fitted to assess the association of between cytokine gene polymorphisms and T2DM. Odds ratio with 95% CI was determined to assess the presence and strength of association between the explanatory variables and outcome variable. A P-value < 0.05 was considered as statistically significant. RESULT Participants carrying the GG genotype of IL-6 (- 174) (OR (95% CI) = 4.61 (2.07-10.54) was a high likelihood of having T2DM compared to those carrying the CC and AA genotypes. AA and AG genotypes of IL-10 (- 1082) were at lower odd of developing T2DM compared to those carrying the GG genotype. In addition, individuals carrying the G allele of IL-6 (- 174) have 2.82-fold odds of developing T2DM compared to individuals carrying the C allele (OR (95% CI) =2.81 (1.78-4.50)). CONCLUSION Our study revealed that genetic polymorphisms of IL-6 (- 174) GG genotype is the potential host genetic risk factors to T2DM. While, IL-10 (- 1082) AA genotype is negatively associated with T2DM. Therefore, IL-6 (- 174) and IL-10 (- 1082) genetic variation may be considered as a biomarker for early screening and diagnosis of T2DM.
Collapse
Affiliation(s)
- Birhanu Ayelign
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
| | - Markos Negash
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Henok Andualem
- Department of Medical Laboratory Science, College of Medicine and Health Sciences, Debretabor University, Debretabor, Ethiopia
| | - Tadelo Wondemagegn
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Eyuel Kassa
- University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia
| | - Tewodros Shibabaw
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Yonas Akalu
- Department of Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| | - Meseret Derbew Molla
- Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
| |
Collapse
|
|
16
|
Martínez-Ramírez OC, Salazar-Piña DA, de Lorena RGM, Castro-Hernández C, Casas-Ávila L, Portillo-Jacobo JA, Rubio J. Association of NFκβ, TNFα, IL-6, IL-1β, and LPL Polymorphisms with Type 2 Diabetes Mellitus and Biochemical Parameters in a Mexican Population. Biochem Genet 2021; 59:940-965. [PMID: 33599871 DOI: 10.1007/s10528-021-10047-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Accepted: 02/02/2021] [Indexed: 10/22/2022]
Abstract
Chronic low-grade inflammation is strongly related to the etiology of diabetes mellitus type 2 (T2DM), and the expression of inflammatory cytokines may be modulated by polymorphisms located in the regulatory regions of the NFκβ, IL-1β, IL-6, TNFα, and LPL genes. We considered it particularly important to investigate the relationship of gene polymorphisms involved in chronic inflammation with the risk of T2DM or uncontrolled biochemical parameters. METHODS We included 199 individuals with a T2DM diagnosis and 213 individuals without a T2DM diagnosis. Restriction fragment length polymorphism (RFLP) analyses were used to assess polymorphisms. RESULTS We found a risk association between T2DM and uncontrolled biochemical parameters in a Mexican population for the genotypes del/del of NFκβ, -174 and -572 of IL-6, C/C of IL-1β, -308 and -238 of TNFα, and T/T of LPL. In subjects without diabetes (controls), we found an association between the G/C genotype of the -572 polymorphism and the G/C and C/C genotypes of the -597 polymorphism of IL-6 with the risk of glucose levels > 131 mg/dL. Genotype C/C of polymorphism -174 of the IL-6 gene was associated with high triglyceride levels, and levels > 5.8% of HbA1c were associated with the G/A genotype of TNFα -308. CONCLUSION Here, we describe for the first time the relationship of T2DM risk and uncontrolled biochemical parameters with polymorphisms in the NFκβ, IL-6, TNFα, IL-1β, and LPL genes in a Mexican population. We also showed that for the population included in this study, there is an additive effect of the polymorphisms of the studied genes that considerably increases the risk of developing T2DM.We also showed that there are interactions between genes related to chronic inflammation that affect the risk of T2DM.
Collapse
Affiliation(s)
- O C Martínez-Ramírez
- Facultad de Nutrición, Universidad Autónoma del Estado de Morelos, Río Iztacihuatl S/N. Col. Vista Hermosa, C.P. 62350, Mexico, Mexico.
| | - D A Salazar-Piña
- Facultad de Nutrición, Universidad Autónoma del Estado de Morelos, Río Iztacihuatl S/N. Col. Vista Hermosa, C.P. 62350, Mexico, Mexico
| | - Ramos-García M de Lorena
- Facultad de Nutrición, Universidad Autónoma del Estado de Morelos, Río Iztacihuatl S/N. Col. Vista Hermosa, C.P. 62350, Mexico, Mexico
| | - C Castro-Hernández
- Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510, Ciudad de México, Mexico
| | - L Casas-Ávila
- Departamento de Genética, Instituto Nacional de Rehabilitación, C.P. 14389, Ciudad de México, Mexico
| | - J A Portillo-Jacobo
- Facultad de Nutrición, Universidad Autónoma del Estado de Morelos, Río Iztacihuatl S/N. Col. Vista Hermosa, C.P. 62350, Mexico, Mexico
| | - J Rubio
- Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, C.P. 04510, Ciudad de México, Mexico
| |
Collapse
|
|
17
|
Kumar V, Singh J, Bala K, Singh J. Association of resistin (rs3745367) and urotensin II (rs228648 and rs2890565) gene polymorphisms with risk of type 2 diabetes mellitus in Indian population. Mol Biol Rep 2020; 47:9489-9497. [PMID: 33269434 DOI: 10.1007/s11033-020-05991-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 11/06/2020] [Indexed: 01/20/2023]
Abstract
Insulin resistance may become the most powerful predictor of future development of type 2 diabetes mellitus (T2DM) and a therapeutic target for the treatment of the same. Both Resistin, an adipose derived peptide hormone and Urotensin II a potent vasoconstrictor, are reported to be involved in the development of insulin resistance and T2DM but the results remain contradictory. Therefore, investigations were carried out to study the association of T2DM and single nucleotide polymorphism (SNP) in Resistin (RETN) gene at rs3745367 (+ 299 G > A) and Urotensin II (UTS2) gene at rs228648 (+ 143 G > A) and rs2890565 (+ 3836 C > T) in a North Indian population. Method: The present case-control study, conducted from August 2017 to July 2020, involved 168 T2DM patients and 102 healthy controls. SNPs rs3745367, rs228648 and rs2890565 were amplified from genomic DNA in the studied samples by polymerase chain reaction (PCR) using specific primers. The amplified products were genotyped by restriction fragment length polymorphism (RFLP) using particular restriction endonucleases. Clinical parameters viz. glycosylated haemoglobin (HbA1c), fasting blood glucose (FBG), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), total cholesterol (CHL) and fasting insulin were determined by enzymatic methods. Result and conclusion: A statistically significant association between T2DM and RETN gene at SNP rs3745367 (p = 0.001) and UTS2 gene at SNP rs2890565 (p = 0.001) was observed. In RETN gene SNP rs3745367, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were found to be higher in GA + AA combined genotype than in GG genotype for T2DM subjects. Regression analysis revealed that SNP rs2890565 and HOMA-IR were independently associated with the risk of development of T2DM when three SNPs were taken as independent variable adjusted for clinical variables. Among four haplotypes, A/T was found associated with increased risk of T2DM as determined for rs228648 and rs2890565 of UTS2 gene. It can be concluded from these results that polymorphism at rs3745367 of RETN gene and at rs2890565 of UTS2 gene are associated with risk of T2DM in North Indian population.
Collapse
Affiliation(s)
- Vikas Kumar
- Department of Biochemistry, Kurukshetra University, Kurukshetra, 136119, India
| | - Jaswinder Singh
- Department of Biochemistry, Kurukshetra University, Kurukshetra, 136119, India
| | - Kiran Bala
- Department of Biochemistry, Kurukshetra University, Kurukshetra, 136119, India
| | - Jasbir Singh
- Department of Biochemistry, Kurukshetra University, Kurukshetra, 136119, India.
| |
Collapse
|
|
18
|
Pastor-Maldonado CJ, Suárez-Rivero JM, Povea-Cabello S, Álvarez-Córdoba M, Villalón-García I, Munuera-Cabeza M, Suárez-Carrillo A, Talaverón-Rey M, Sánchez-Alcázar JA. Coenzyme Q 10: Novel Formulations and Medical Trends. Int J Mol Sci 2020; 21:E8432. [PMID: 33182646 PMCID: PMC7697799 DOI: 10.3390/ijms21228432] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Revised: 10/31/2020] [Accepted: 11/07/2020] [Indexed: 12/11/2022] Open
Abstract
The aim of this review is to shed light over the most recent advances in Coenzyme Q10 (CoQ10) applications as well as to provide detailed information about the functions of this versatile molecule, which have proven to be of great interest in the medical field. Traditionally, CoQ10 clinical use was based on its antioxidant properties; however, a wide range of highly interesting alternative functions have recently been discovered. In this line, CoQ10 has shown pain-alleviating properties in fibromyalgia patients, a membrane-stabilizing function, immune system enhancing ability, or a fundamental role for insulin sensitivity, apart from potentially beneficial properties for familial hypercholesterolemia patients. In brief, it shows a remarkable amount of functions in addition to those yet to be discovered. Despite its multiple therapeutic applications, CoQ10 is not commonly prescribed as a drug because of its low oral bioavailability, which compromises its efficacy. Hence, several formulations have been developed to face such inconvenience. These were initially designed as lipid nanoparticles for CoQ10 encapsulation and distribution through biological membranes and eventually evolved towards chemical modifications of the molecule to decrease its hydrophobicity. Some of the most promising formulations will also be discussed in this review.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - José A. Sánchez-Alcázar
- Centro Andaluz de Biología del Desarrollo (CABD-CSIC-Universidad Pablo de Olavide), and Centro de Investigación Biomédica en Red: Enfermedades Raras, Instituto de Salud Carlos III. Universidad Pablo de Olavide, 41013 Sevilla, Spain; (C.J.P.-M.); (J.M.S.-R.); (S.P.-C.); (M.Á.-C.); (I.V.-G.); (M.M.-C.); (A.S.-C.); (M.T.-R.)
| |
Collapse
|
|
19
|
The Chemical Composition of Brazilian Green Propolis and Its Protective Effects on Mouse Aortic Endothelial Cells against Inflammatory Injury. Molecules 2020; 25:molecules25204612. [PMID: 33050458 PMCID: PMC7587206 DOI: 10.3390/molecules25204612] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 09/28/2020] [Accepted: 10/03/2020] [Indexed: 11/16/2022] Open
Abstract
Propolis has a very complex composition, with antibacterial, anti-inflammatory and other properties. To determine the composition of ethanol extracts of Brazilian green propolis (EEP-B) and their protective effect on mouse aortic endothelial cells (MAECs), the chemical composition of EEP-B was analysed by UPLC/Q-TOF-MS/MS, and the protective effect of EEP-B on the proliferation of lipopolysaccharide (LPS)-induced MAECs was determined by Cell Counting Kit-8 (CCK-8) assays. The protein levels of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA), and ICAM-1, VCAM-1 and MCP-1 expressions were analysed by western blotting. The results showed that a total of 24 compounds belonging to cinnamic acids and flavonoids, including 3,5-diisopentenyl-4-hydroxycinnamic acid (artepillin C), kaempferide, 3-isoprenyl p-coumaric acid, pinocembrin and 4′-methoxy pinobanksin, were identified in EEP-B. Among them, a new component, suggested to be 5-isoprenyl caffeic acid p-coumaric acid ester, was reported for the first time. The LPS-induced levels of TNF-α, IL-6, ICAM-1, VCAM-1 and MCP-1 were downregulated in response to 5, 10 and 20 μg/mL EEP-B. This study revealed that EEP-B could reduce LPS-induced inflammatory reactions, improve cell survival, and protect MAECs by regulating ICAM-1, VCAM-1 and MCP-1 expression. These findings could provide a theoretical basis for MAEC treatment using EEP-B.
Collapse
|
|
20
|
Shah P, Chavda V, Patel S, Bhadada S, Ashraf GM. Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies. Curr Gene Ther 2020; 20:223-235. [DOI: 10.2174/1566523220999200726225457] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 05/28/2020] [Accepted: 07/14/2020] [Indexed: 01/01/2023]
Abstract
Background:
Postprandial hyperglycemia considered to be a major risk factor for
cerebrovascular complications.
Objective:
The current study was designed to elucidate the beneficial role of voglibose via in-silico in
vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone
type 2 diabetes.
Material and Methods:
In-Silico molecular docking and virtual screening were carried out with the
help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the
results of docking studies, in-vivo investigation was carried out for possible neuroprotective action.
T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after
induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks,
diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery,
neurological deficits were determined. The blood was collected for the determination of serum
glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct
volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels,
and aldose reductase activity.
Results:
In-silico docking studies showed good docking binding score for stroke associated proteins,
which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study,
pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels.
Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the
difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced
significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+
ATPase, oxidative stress, and aldose reductase activity in brain homogenate.
Conclusion:
In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo
induced stroke, animal model outcomes support the strong anti-stroke signature for possible
neuroprotective therapeutics.
Collapse
Affiliation(s)
- Pooja Shah
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmadabad, Gujarat, 382 481, India
| | - Vishal Chavda
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmadabad, Gujarat, 382 481, India
| | - Snehal Patel
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmadabad, Gujarat, 382 481, India
| | - Shraddha Bhadada
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmadabad, Gujarat, 382 481, India
| | - Ghulam Md. Ashraf
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| |
Collapse
|
|
21
|
Maluf S, Salgado JV, Cysne DN, Camelo DMF, Nascimento JR, Maluf BVT, Silva LDM, Belfort MRDC, Silva LA, Guerra RNM, Salgado Filho N, Nascimento FRF. Increased Glycated Hemoglobin Levels in Patients With Helicobacter pylori Infection Are Associated With the Grading of Chronic Gastritis. Front Immunol 2020; 11:2121. [PMID: 33013895 PMCID: PMC7511518 DOI: 10.3389/fimmu.2020.02121] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 08/05/2020] [Indexed: 12/20/2022] Open
Abstract
Background Recent studies have found an association between Helicobacter pylori infection and prediabetes. Whether H. pylori per se or host factors are involved in the disturbance of glycated hemoglobin needs further investigation. The aim of this study was to determine the association of glycated hemoglobin levels with endoscopic diagnosis and the inflammatory response in H. pylori infection. Methods A cross-sectional study was carried out in 88 dyspeptic non-diabetic adults who underwent esophagogastroduodenoscopy. The diagnosis of H. pylori infection was performed through urease test and histopathological exam. Cases were initially distributed into two groups: control (without H. pylori infection, n = 22) and HP (patients with H. pylori infection, n = 66). HbA1c was measured to determine prediabetes status according to the American Diabetes Association criteria, and then the groups were subdivided into non-prediabetic (n = 14), prediabetic (n = 8), non-prediabetic HP (n = 26) and prediabetic HP (n = 40) groups. Gastric mucosa was histologically evaluated to determine H. pylori density and inflammatory activity according to Sydney System. To investigate the balance of anti-inflammatory and pro-inflammatory cytokines we measured interleukin 10 (anti-inflammatory) and Tumor Necrosis Factor-a (pro-inflammatory) in the plasma or in the gastric mucosa. Results Patients with H. pylori infection had higher mean HbA1c levels than those without H. pylori infection. However, increased HbA1c levels were not associated with H. pylori-related factors but with the bacterial density, the intensity of inflammation and the activity of the chronic gastritis. In addition, H. pylori infection per se did not alter IL-10 and TNF-α neither in the plasma nor in the gastric mucosa, but the bacterial density was negatively correlated with systemic and local IL-10 expression. Although no correlation was found between systemic cytokines and HbA1c levels, local anti-inflammatory cytokine was correlated with HbA1c levels. Conclusion Long-term H. pylori infection is associated with prediabetes. This association is not related to the presence of H. pylori per se but depends on the extent of bacterial colonization and the degree of both local inflammation and activity of the chronic gastritis.
Collapse
Affiliation(s)
- Selma Maluf
- Health Science Graduate Program, Federal University of Maranhão, São Luís, Brazil.,Gastroenterology Service of the University Hospital, Federal University of Maranhão, São Luís, Brazil.,Immunophysiology Laboratory, Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| | - João Victor Salgado
- Department of Physiological Sciences, Federal University of Maranhão, São Luís, Brazil
| | - Dalila Nunes Cysne
- Immunophysiology Laboratory, Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| | | | - Johnny Ramos Nascimento
- Health Science Graduate Program, Federal University of Maranhão, São Luís, Brazil.,Immunophysiology Laboratory, Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| | - Bianca Vitória T Maluf
- Immunophysiology Laboratory, Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| | | | | | - Lucilene Amorim Silva
- Immunophysiology Laboratory, Department of Pathology, Federal University of Maranhão, São Luís, Brazil.,Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| | - Rosane Nassar Meireles Guerra
- Immunophysiology Laboratory, Department of Pathology, Federal University of Maranhão, São Luís, Brazil.,Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| | | | - Flávia Raquel F Nascimento
- Immunophysiology Laboratory, Department of Pathology, Federal University of Maranhão, São Luís, Brazil.,Department of Pathology, Federal University of Maranhão, São Luís, Brazil
| |
Collapse
|
|
22
|
Kushwah AS, Gupta MK, Singh R, Banerjee M. Cytokine gene variants and treatment outcome of cisplatin-based concomitant chemoradiotherapy in cervical cancer. Br J Biomed Sci 2020; 77:81-86. [DOI: 10.1080/09674845.2020.1714164] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- AS Kushwah
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, India
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
| | - MK Gupta
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, India
| | - R Singh
- Department of Obstetrics & Gynecology, King George’s Medical University, Lucknow, India
| | - M Banerjee
- Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, India
| |
Collapse
|
|
23
|
Cardoso NS, Ribeiro VB, Dutra SGV, Ferriani RA, Gastaldi AC, de Araújo JE, de Souza HCD. Polycystic ovary syndrome associated with increased adiposity interferes with serum levels of TNF-alpha and IL-6 differently from leptin and adiponectin. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2020; 64:4-10. [PMID: 32187268 PMCID: PMC10522288 DOI: 10.20945/2359-3997000000197] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 08/28/2019] [Indexed: 11/23/2022]
Abstract
Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10.
Collapse
Affiliation(s)
- Nathália Sigilló Cardoso
- Departamento de Biomecânica, Medicina e Reabilitação do Aparelho LocomotorFaculdade de Medicina de Ribeirão PretoUniversidade de São PauloRibeirão PretoSPBrasilDepartamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brasil
| | - Victor Barbosa Ribeiro
- Departamento de Ginecologia e ObstetríciaFaculdade de Medicina de Ribeirão PretoUniversidade de São PauloRibeirão PretoSPBrasilDepartamento de Ginecologia e Obstetrícia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brasil
- Instituto Federal de São PauloJacareíSPBrasilInstituto Federal de São Paulo, Jacareí, SP, Brasil
| | - Sabrina Graziani Veloso Dutra
- Departamento de Biomecânica, Medicina e Reabilitação do Aparelho LocomotorFaculdade de Medicina de Ribeirão PretoUniversidade de São PauloRibeirão PretoSPBrasilDepartamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brasil
| | - Rui Alberto Ferriani
- Departamento de Ginecologia e ObstetríciaFaculdade de Medicina de Ribeirão PretoUniversidade de São PauloRibeirão PretoSPBrasilDepartamento de Ginecologia e Obstetrícia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brasil
| | - Ada Clarice Gastaldi
- Departamento de Biomecânica, Medicina e Reabilitação do Aparelho LocomotorFaculdade de Medicina de Ribeirão PretoUniversidade de São PauloRibeirão PretoSPBrasilDepartamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brasil
| | - João Eduardo de Araújo
- Departamento de Biomecânica, Medicina e Reabilitação do Aparelho LocomotorFaculdade de Medicina de Ribeirão PretoUniversidade de São PauloRibeirão PretoSPBrasilDepartamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brasil
| | - Hugo Celso Dutra de Souza
- Departamento de Biomecânica, Medicina e Reabilitação do Aparelho LocomotorFaculdade de Medicina de Ribeirão PretoUniversidade de São PauloRibeirão PretoSPBrasilDepartamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brasil
| |
Collapse
|
|
24
|
Ge Q, Feng F, Liu L, Chen L, Lv P, Ma S, Chen K, Yao Q. RNA-Seq analysis of the pathogenesis of STZ-induced male diabetic mouse liver. J Diabetes Complications 2020; 34:107444. [PMID: 31757765 DOI: 10.1016/j.jdiacomp.2019.107444] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 08/31/2019] [Accepted: 09/05/2019] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The liver is a key organ involved in glucose metabolism, and the major target proteins' changes in the pathogenesis are still unknown. METHODS A diabetic mouse model was induced by intraperitoneal injection of streptozotocin (STZ) solution and the RNA-Seq analysis was used to evaluate the transcription differences in the livers of diabetic mice of this study. And then, the differentially expressed genes were validated between a normal mouse group (n = 6) and a diabetic mouse group (n = 6) using quantitative real-time PCR (qRT-PCR) and Western blotting analysis. In addition, we also constructed protein-protein interacting (PPI) networks of up-regulated and down-regulated genes. RESULTS Transcriptome sequencing analysis revealed 370 up-regulated differentially expressed genes and 281 down-regulated differentially expressed genes in the diabetes model. The gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results showed that the differentially expressed genes were mainly involved in immunity, enzyme activity, metabolism, and steroid synthesis. PPI analysis results indicated that the main 15 core differential proteins (Cyp51a1, Acsl4, Ugt1a1, Stat1, Gsta2, Cbr1, Aldh1a1, Fasn, Ces1, Camk2b, Tap1, Egr1, Sqle, Lpin1, Fabp5) were involved in the pathogenesis of diabetes. The qRT-PCR results showed that expression changes of four genes (Acsl4, Stat1, Gsta2, Fabp5) were in different directions from those of RNA-Seq. Western blotting results indicated that Sqle expression change at the protein level was in opposition direction from qRT-PCR, and we speculated that Sqle may be involved in the post-transcriptional modification process. CONCLUSIONS Our data speculated that the pathogenesis of diabetes may be mediated mainly through steroid biosynthesis, metabolic processes, and immune responses. Further researches on these pathways may provide new targets for the prevention and treatment of diabetes.
Collapse
Affiliation(s)
- Qi Ge
- School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Fan Feng
- The Fourth Affiliated Hospital of Jiangsu University, 20# Zhengdong Road, Zhenjiang, Jiangsu 212001, PR China
| | - Lanlan Liu
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Liang Chen
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Peng Lv
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Shangshang Ma
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China
| | - Keping Chen
- Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
| | - Qin Yao
- School of the Environment and Safety Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
| |
Collapse
|
|
25
|
Tu J, Yang Y, Zhang J, Lu G, Ke L, Tong Z, Kasimu M, Hu D, Xu Q, Li W. Regulatory effect of chemerin and therapeutic efficacy of chemerin‑9 in pancreatogenic diabetes mellitus. Mol Med Rep 2020; 21:981-988. [PMID: 31922216 PMCID: PMC7002998 DOI: 10.3892/mmr.2020.10915] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 10/02/2019] [Indexed: 12/13/2022] Open
Abstract
Chemerin is a novel adipokine that regulates immune responses, adipocyte differentiation, and glucose metabolism. However, the role of chemerin in pancreatogenic diabetes mellitus (PDM) remains unknown. PDM is recognized as DM occurring secondary to chronic pancreatitis or pancreatic resection due to the loss of the loss of islet cell mass. The aim of the present study was to investigate the role of chemerin in PDM by collecting blooding samples from DM patients and establishing in vivo PDM model. The present study demonstrated that chemerin levels are decreased in the serum of patients with PDM and are negatively associated with the insulin resistance (IR) status. Chemerin levels also decreased during the development of PDM in C57BL/6 mice, together with increasing serum levels of interleukin-1 and tumor necrosis factor-α and decreasing mRNA expression levels of glucose transporter 2 (GLUT2) and pancreatic and duodenal homeobox 1 (PDX1). Treatment of PDM model mice with chemerin chemokine-like receptor 1 (CMKLR1) agonist, chemerin-9, elevated the serum levels of chemerin and mRNA expression levels of GLUT2 and PDX1, leading to the alleviation of glucose intolerance and IR in these animals. Together, the accumulated data indicated that chemerin may exert a protective function in PDM, perhaps by regulating perhaps by regulating GLUT2 and PDX1 expression, and that the restoration of the chemerin/CMKLR1 pathway may represent a novel therapeutic strategy for PDM.
Collapse
Affiliation(s)
- Jianfeng Tu
- Department of General Surgery, Akesu First People's Hospital, Akesu, Xinjiang 843000, P.R. China
| | - Yue Yang
- Hangzhou Medical College, Hangzhou, Zhejiang 310053, P.R. China
| | - Jingzhu Zhang
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Guotao Lu
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Lu Ke
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Zhihui Tong
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| | - Maimaitijiang Kasimu
- Department of General Surgery, Akesu First People's Hospital, Akesu, Xinjiang 843000, P.R. China
| | - Dejun Hu
- Department of General Surgery, Akesu First People's Hospital, Akesu, Xinjiang 843000, P.R. China
| | - Qiuran Xu
- Department of Emergency Medicine, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
| | - Weiqin Li
- Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P.R. China
| |
Collapse
|
|
26
|
Tatsch E, De Carvalho JAM, Bollick YS, Duarte T, Duarte MMMF, Vaucher RA, Premaor MO, Comim FV, Moresco RN. Low frataxin mRNA expression is associated with inflammation and oxidative stress in patients with type 2 diabetes. Diabetes Metab Res Rev 2020; 36:e3208. [PMID: 31343823 DOI: 10.1002/dmrr.3208] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 06/04/2019] [Accepted: 07/16/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND The mitochondrial protein frataxin is involved in iron metabolism, as well as regulation of oxidative stress. To elucidate the association of frataxin with the pathophysiology of diabetes, we evaluated the mRNA levels of frataxin in leukocytes of patients with type 2 diabetes (T2D). In addition, we investigated the relation between frataxin mRNA levels, inflammatory cytokines, and oxidative stress biomarkers. METHODS A study including 150 subjects (115 patients with T2D and 35 healthy subjects) was performed to evaluate the frataxin mRNA levels in leukocytes. We assessed the relation between frataxin and interleukin (IL)-6, IL-1, tumour necrosis factor-alpha (TNF-α), total oxidation status (TOS), total antioxidant capacity (TAC), and serum iron. RESULTS The frataxin mRNA levels in the T2D group were significantly lower than those in healthy subjects. It was also demonstrated that T2D patients with frataxin mRNA levels in the lowest quartile had significantly elevated levels of serum iron, TOS, and inflammatory cytokines, such as TNF-α, IL-1, and IL-6, while TAC levels were significantly lower in this quartile when compared with the upper quartile. CONCLUSIONS Our findings showed that T2D patients with low frataxin mRNA levels showed a high degree of inflammation and oxidative stress. It is speculated that frataxin deficiency in T2D patients can contribute to the imbalance in mitochondrial iron homeostasis leading to the acceleration of oxidative stress and inflammation.
Collapse
Affiliation(s)
- Etiane Tatsch
- Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - José A M De Carvalho
- Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Santa Maria, Santa Maria, RS, Brazil
- Laboratory of Clinical Analysis, University Hospital, Santa Maria, RS, Brazil
| | - Yãnaí S Bollick
- Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Thiago Duarte
- Laboratory of Biogenomic, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Marta M M F Duarte
- Department of Health Sciences, Lutheran University of Brazil, Santa Maria, RS, Brazil
| | - Rodrigo A Vaucher
- Center of Chemical, Pharmaceutical and Food Sciences, Federal University of Pelotas, Pelotas, RS, Brazil
| | - Melissa O Premaor
- Department of Clinical Medicine, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Fabio V Comim
- Department of Clinical Medicine, Federal University of Santa Maria, Santa Maria, RS, Brazil
| | - Rafael N Moresco
- Laboratory of Clinical Biochemistry, Department of Clinical and Toxicological Analysis, Federal University of Santa Maria, Santa Maria, RS, Brazil
| |
Collapse
|
|
27
|
Saxena M, Ali D, Modi DR, Almarzoug MHA, Hussain SA, Manohrdas S. Association of TNF-α Gene Expression and Release in Response to Anti-Diabetic Drugs from Human Adipocytes in vitro. Diabetes Metab Syndr Obes 2020; 13:2633-2640. [PMID: 32801814 PMCID: PMC7399456 DOI: 10.2147/dmso.s265362] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 07/02/2020] [Indexed: 11/23/2022] Open
Abstract
INTRODUCTION TNF-α, a proinflammatory cytokine secreted by activated immune cells, and overexpression of it in adipocytes, has an important role in insulin resistance progression and diabetes development. AIM AND OBJECTIVE Subcutaneous adipocytes derived from mesenchymal stem cells were used for in vitro analysis to find the role of antidiabetic drugs on TNF-α in high glucose-fed adipocytes. METHODS In vitro adipocytes were used along with variable concentration of anti-diabetic drugs. The level of TNF-α was measured by ELISA and the mRNA level was quantified using SYBR-Green real-time PCR. All data were statistically analyzed. RESULTS The level of TNF-α and the mRNA expression were observed and analyzed with normal adipocytes. TNF-α level and expression of it showed agonistic behavior, ie no change at low concentration while enhances with the increase of glucose. The level was decreased significantly when the adipocytes were treated with metformin (p=0.015) and pioglitazone (p=0.020). A combination of drugs showed that the expression of TNF-α was almost the same as for metformin alone. However, insulin increases the TNF-α expression as for pioglitazone. DISCUSSION Such a report on adipocytes may be helpful for clinical benefits to understand the additional mechanism of adipocytes on the release and expression of TNF-α. However, anti-diabetic drugs including insulin up-regulate the TNF-α gene expression in mild or severe glucose load.
Collapse
Affiliation(s)
- Madhukar Saxena
- Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
- Correspondence: Madhukar Saxena Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Rai Bareilly Road, Lucknow, India Email
| | - Daoud Ali
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Dinesh Raj Modi
- Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
| | | | - S A Hussain
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - S Manohrdas
- Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia
| |
Collapse
|
|
28
|
The association of TNF-α -308G/A and -238G/A polymorphisms with type 2 diabetes mellitus: a meta-analysis. Biosci Rep 2019; 39:221417. [PMID: 31803921 PMCID: PMC6923338 DOI: 10.1042/bsr20191301] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 10/31/2019] [Accepted: 12/04/2019] [Indexed: 12/24/2022] Open
Abstract
Tumor necrosis factor-α (TNF-α) is involved in insulin resistance and has long been a candidate gene implicated in type 2 diabetes mellitus (T2DM), however the association between TNF-α polymorphisms -308G/A and -238G/A and T2DM remains controversial. The present study sought to verify associations between these polymorphisms and T2DM susceptibility using a meta-analysis approach. A total of 49 case-control studies were selected up to October 2018. Statistical analyses were performed by STATA 15.0 software. The odds ratios (ORs) and 95% confidence intervals were calculated to estimate associations. Meta-analyses revealed significant associations between TNF-α -308G/A and T2DM in the allele model (P=0.000); the dominant model (P=0.000); the recessive model (P=0.001); the overdominant model (P=0.008) and the codominant model (P=0.000). Subgroup analyses also showed associations in the allele model (P=0.006); the dominant model (P=0.004) and the overdominant model (P=0.005) in the Caucasian and in the allele model (P=0.007); the dominant model (P=0.014); the recessive model (P=0.000) and the codominant model (P=0.000) in the Asian. There were no associations between TNF-α -238G/A and T2DM in the overall and subgroup populations. Meta-regression, sensitivity analysis and publication bias analysis confirmed that results and data were statistically robust. Our meta-analysis suggests that TNF-α -308G/A is a risk factor for T2DM in Caucasian and Asian populations. It also indicates that TNF-α -238G/A may not be a risk factor for T2DM. More comprehensive studies will be required to confirm these associations.
Collapse
|
|
29
|
Venugopal G, O'Regan NL, Babu S, Schumann RR, Srikantam A, Merle R, Hartmann S, Steinfelder S. Association of a PD-L2 Gene Polymorphism with Chronic Lymphatic Filariasis in a South Indian Cohort. Am J Trop Med Hyg 2019; 100:344-350. [PMID: 30594267 DOI: 10.4269/ajtmh.18-0731] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Lymphatic filariasis (LF) is a parasitic infection, caused by three closely related nematodes, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. Previously, we have shown that lysate from B. malayi microfilariae induces the expression of interleukin (IL)-10 and programmed death-ligand (PD-L) 1 on monocytes, which lead to inhibition of CD4+ T-cell responses. In this study, we investigated associations of IL-10 and programmed cell death (PD)-1 pathway gene polymorphisms with clinical manifestation in LF. We evaluated the frequency of alleles and genotypes of IL-10 (rs3024496, rs1800872), IL-10RA (rs3135932), IL-10RB (rs2834167), PD-1 (rs2227982, rs10204525), PD-L1 (rs4143815), PD-L2 (rs7854413), and single-nucleotide polymorphisms (SNPs) in 103 patients with chronic pathology (CP), such as elephantiasis or hydrocele and 106 endemic normal (EN) individuals from a South Indian population living in an area endemic for LF. Deviations from the Hardy-Weinberg equilibrium were tested, and we found a significant difference between the frequency of polymorphisms in PD-L2 (rs7854413; P < 0.001) and IL-10RB (rs2834167; P = 0.012) between the CP and the EN group, whereas there were no significant differences found among IL-10, IL-10RA, PD-1, and PD-L1 SNPs. A multivariate analysis showed that the existence of a CC genotype in PD-L2 SNP rs7854413 is associated with a higher risk of developing CP (OR: 2.942; 95% confidence interval [CI]: 0.957-9.046; P = 0.06). Altogether, these data indicate that a genetically determined individual difference in a non-synonymous missense SNP of PD-L2 might influence the susceptibility to CP.
Collapse
Affiliation(s)
- Gopinath Venugopal
- Centre for Infection Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany
| | - Noëlle L O'Regan
- Centre for Infection Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany
| | - Subash Babu
- National Institutes of Health, National Institute of Research in Tuberculosis (NIRT), International Centre for Excellence in Research, Chennai, India
| | - Ralf R Schumann
- Institute for Microbiology and Hygiene, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Aparna Srikantam
- Blue Peter Public Health and Research Centre, LEPRA Society, Hyderabad, India
| | - Roswitha Merle
- Department of Veterinary Medicine, Institute for Veterinary Epidemiology and Biostatistics, Freie Universität Berlin, Berlin, Germany
| | - Susanne Hartmann
- Centre for Infection Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany
| | - Svenja Steinfelder
- Centre for Infection Medicine, Institute of Immunology, Freie Universität Berlin, Berlin, Germany.,Department of Neural Circuits and Behavior, Max Delbrück Center for Molecular Medicine, Berlin, Germany
| |
Collapse
|
|
30
|
Banerjee M, Vats P, Kushwah AS, Srivastava N. Interaction of antioxidant gene variants and susceptibility to type 2 diabetes mellitus. Br J Biomed Sci 2019; 76:166-171. [PMID: 30900957 DOI: 10.1080/09674845.2019.1595869] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background: Diabetes is the seventh most common disease leading to death with a global estimate of 425 million diabetics, expected to be 629 million in 2045. The role of reactive metabolites and antioxidants, such as glutathione, glutathione peroxidase, superoxide dismutase and catalase in type 2 diabetes mellitus (T2DM) provides an opportunity for identifying gene variants and risk genotypes. We hypothesised that certain antioxidant gene-gene interactions are linked with T2DM and can model disease risk prediction.Materials and methods: Genotyping of single nucleotide polymorphisms (SNPs) in antioxidant genes for glutathione (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) was performed in 558 T2DMs and 410 age and sex matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), routine lab indices by standard techniques.Results: The null/null allele combination of GSTM1del and GSTT1del increased disease risk up to 1.7-fold. The combination of SNPs in GSTM1del, GSTT1del, GSTP1 + 313A/G and in CAT-21A/T, SOD2 + 47C/T, GPx1 + 599C/T increased the risk of diabetes 13.5 and 2.1-fold, respectively. Interaction of SNPs GSTM1del, GSTT1del, GSTP1 + 313A/G (105Ile/Val), CAT-21A/T, SOD2 + 47C/T, GPx1 + 599C/T were significantly linked with disease risk >5 × 103 fold.Conclusion: As the number of gene combinations increase, there is a rise in the odds ratio of disease risk, suggesting that gene-gene interaction plays an important role in T2DM susceptibility. Individuals who possess the GSTM1del, GSTT1del, GSTP1 105I/V(+313A/G), CAT-21A/T, SOD2 + 47C/T and GPx1 + 599C/T are at very high risk of developing T2DM.
Collapse
Affiliation(s)
- M Banerjee
- Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India
| | - P Vats
- Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India
| | - A S Kushwah
- Molecular & Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow, Uttar Pradesh, India.,Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - N Srivastava
- Department of Physiology, King George's Medical University, Lucknow, Uttar Pradesh, India
| |
Collapse
|
|
31
|
Lara-Gómez RE, Moreno-Cortes ML, Muñiz-Salazar R, Zenteno-Cuevas R. Association of polymorphisms at -174 in IL-6, and -308 and -238 in TNF-α, in the development of tuberculosis and type 2 diabetes mellitus in the Mexican population. Gene 2019; 702:1-7. [PMID: 30917933 DOI: 10.1016/j.gene.2019.03.050] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 03/20/2019] [Accepted: 03/21/2019] [Indexed: 01/04/2023]
Abstract
Polymorphisms at -176 in IL-6, and -238 and -308 in TNF-α have been described as risk factors for developing tuberculosis (TB) and type 2 diabetes mellitus (T2DM). However, it is not known how these changes influence the development of TB-T2DM comorbidity. The objective of this work was therefore to analyze the impact of these polymorphisms in the Mexican population. This is a cross-sectional study of cases and controls in which polymorphisms at -174 in IL-6, -238 and -308 in TNF-α were identified in healthy subjects, those with TB, T2DM and carriers of the comorbidity, each group consisted of 30 individuals. Descriptions of the population, frequency of genotypes and risk association were calculated, and a reduction of multifactorial dimensionality between groups (MDR) was determined. Genotype 174 G/G-of IL-6 was observed in 78% of individuals, while -308 G/G and -238 G/G of TNF-α occurred in 90% and 91% of individuals, respectively. The -174 G/G IL-6 in individuals with T2DM increased five-fold (p = .02) the risk of developing the comorbidity. The MDR analysis showed that the association of -174 G/G IL-6 and -308 G/G TNF-α in healthy individuals increased the risk of developing the comorbidity up to six-fold (p = .019), while in individuals with T2DM, this risk augmented 14-fold (p = .0002). The -174 G/G IL-6 genotype increases the risk of developing comorbidity in the T2DM population and this risk is raised when associated with -308 G/G TNF-α. These findings have implications for understanding the epidemiological dynamics of the TB-T2DM comorbidity, promoting prevention strategies and inhibiting the development of this co-morbidity.
Collapse
Affiliation(s)
- Ruth Elizabeth Lara-Gómez
- Instituto de Salud Pública, Universidad Veracruzana, Jalapa, Veracruz, Mexico; Programa de Doctorado en Ciencias de la Salud, Instituto de Ciencias de la Salud, Universidad Veracruzana, Jalapa, Veracruz, Mexico
| | - María Luisa Moreno-Cortes
- Área de Biomedicina, Instituto de Investigaciones Biológicas, Universidad Veracruzana, Jalapa, Veracruz, Mexico
| | - Raquel Muñiz-Salazar
- Laboratorio de Epidemiología y Ecología y Molecular, Escuela de Ciencias de la Salud, Universidad Autónoma de Baja California, Ensenada, Baja California, Mexico
| | | |
Collapse
|
|
32
|
Kang J, Liu CH, Lee CN, Li HY, Yang CW, Huang SC, Lin SY, Jou TS. Novel Interleukin-10 Gene Polymorphism Is Linked to Gestational Diabetes in Taiwanese Population. Front Genet 2019; 10:89. [PMID: 30873205 PMCID: PMC6401599 DOI: 10.3389/fgene.2019.00089] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 01/29/2019] [Indexed: 11/24/2022] Open
Abstract
Objective: The association of interleukin-10 (IL-10) polymorphism with diabetes and its complication was recently established, while there were few researches considering the potential role of IL-10 in gestational diabetes (GDM). This study aimed to investigate the association between IL-10 gene rs1800896 (−1082 A/G), rs1800871 (−819 T/C), rs1800872 (−592 A/C), and rs3021094 (3388 A/C) single nucleotide polymorphisms (SNPs) and GDM susceptibility. Methods: This study included 72 GDM patients and 100 healthy pregnant women. Direct sequencing of the products from polymerase chain reactions of the extracted genomic DNA from study subjects were conducted for analyzing IL-10 gene polymorphism and further genotype frequencies were compared. Plasma IL-10 concentration was measured by ELISA method. Results: The results revealed no significant difference in −592 A/C, −819 T/C, and −1082 A/G genotypes. Significantly increased prevalence of A allele (P = 0.028, OR = 1.69, 95% CI = 1.081–2.64) and A/A genotype (P = 0.031, OR = 2.881, 95% CI = 1.145–7.250) at a previously un-characterized rs3021094 SNP were discovered in the GDM group. Increased IL-10 levels and insulin resistance were also related to the genotype of rs3021094. The risk of GDM was increased when IL-10 level was over 6.5 pg/ml. Conclusion: Our study demonstrated that A allele and A/A genotype of rs3021094 SNP in IL-10 gene were linked to increased risk for GDM, IL-10 plasma level and insulin resistance, which could be potential targets for early screening and detection of GDM.
Collapse
Affiliation(s)
- Jessica Kang
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Hsiung Liu
- Department of Surgery, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Chien-Nan Lee
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Yuan Li
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Wen Yang
- Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shu-Chien Huang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Shin-Yu Lin
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Tzuu-Shuh Jou
- Graduate Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Center of Precision Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
33
|
Cho Y, Mitchell R, Paudel S, Feltham T, Schon L, Zhang Z. Compromised Antibacterial Function of Multipotent Stromal Cells in Diabetes. Stem Cells Dev 2019; 28:268-277. [DOI: 10.1089/scd.2018.0219] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
- Young Cho
- Orthobiologic Laboratory, MedStar Union Memorial Hospital, Baltimore, Maryland
| | - Reed Mitchell
- Orthobiologic Laboratory, MedStar Union Memorial Hospital, Baltimore, Maryland
| | - Sharada Paudel
- Orthobiologic Laboratory, MedStar Union Memorial Hospital, Baltimore, Maryland
| | - Tyler Feltham
- Orthobiologic Laboratory, MedStar Union Memorial Hospital, Baltimore, Maryland
| | - Lew Schon
- Orthobiologic Laboratory, MedStar Union Memorial Hospital, Baltimore, Maryland
| | - Zijun Zhang
- Orthobiologic Laboratory, MedStar Union Memorial Hospital, Baltimore, Maryland
| |
Collapse
|
|
34
|
Ayelign B, Genetu M, Wondmagegn T, Adane G, Negash M, Berhane N. TNF-α (-308) Gene Polymorphism and Type 2 Diabetes Mellitus in Ethiopian Diabetes Patients. Diabetes Metab Syndr Obes 2019; 12:2453-2459. [PMID: 31819571 PMCID: PMC6886533 DOI: 10.2147/dmso.s229987] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 11/21/2019] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a metabolic disorder resulting from insulin insufficiency or function. Predisposing factors for T2DM are mainly genetic and environmental. Genetic polymorphism of cytokines like tumor necrosis factor-alpha (TNF-α) is suggestive of interference with insulin-sensitive glucose uptake and induces insulin resistance that ultimately could lead to T2DM. In this study, we assessed the effect of TNF-α (-308) G/A gene polymorphism and its association with the development of T2DM in an Ethiopian population. METHODS An institutional-based cross-sectional study was conducted on study subjects with T2DM and non-diabetic healthy controls. DNA was extracted and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction. A genetic-polymorphism on TNF-α (-308) G/A with T2DM was evaluated by logistic regression and Student's t-test. A P-value <0.05 was considered as statistically significant. RESULTS In the present study, we observed a significant association between T2DM and TNF-α (-308) gene polymorphism's GG genotype [χ2 test P = 0.005, OR (95% CI) =2.667 (1.309-5.45d8)]. In contrast, no statistically significant differences were observed in the frequencies of genotypes AA and AG (χ2 test P=0.132 and 0.067, respectively). Moreover, T2DM individuals had higher concentrations of lipid profiles for those carrying the TNF-α (-308) GG genotype as compared to the control group. CONCLUSION TNF-α (-308) genetic polymorphism may be implicated in the genetic susceptibility for, as well as the development of T2DM and lipid metabolism in the Ethiopian population. Therefore, a large-scale study and early screening of TNF-α (-308) genetic polymorphism may help in early management and control of diabetes and related outcomes.
Collapse
Affiliation(s)
- Birhanu Ayelign
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopa
- Correspondence: Birhanu Ayelign Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopa Email
| | - Meaza Genetu
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopa
| | - Tadelo Wondmagegn
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopa
| | - Gashaw Adane
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopa
| | - Markos Negash
- Department of Immunology and Molecular Biology, School of Biomedical and Laboratory Science, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopa
| | - Nega Berhane
- Institute of Biotechnology, College of Computational and Natural Science, University of Gondar, Gondar, Ethiopa
| |
Collapse
|
|
35
|
Asadikaram G, Ram M, Izadi A, Sheikh Fathollahi M, Nematollahi MH, Najafipour H, Shahoozehi B, Mirhoseini M, Masoumi M, Shahrokhi N, Arababadi MK. The study of the serum level of IL-4, TGF-β, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension. J Cell Biochem 2018; 120:4147-4157. [PMID: 30260038 DOI: 10.1002/jcb.27700] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 08/27/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Obesity increases the risk of diabetes mellitus (DM) and hypertension. We aimed to analyze the serum levels of cytokines that have relevance to the pathologies including, interleukin-4 (IL-4), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), and IL-6 cytokines of overweight men with DM and/or hypertension. METHODS The study collected serum from 164 men. The sample population contained, 54 overweight men without DM or hypertension (control [CTL] group), 36 men with both DM and hypertension (DH group), 20 men with DM but no hypertension (D group), and 54 had hypertension without DM (H). RESULTS The main results showed that the concentration of IFN-γ in the DH group was significantly higher than the D, H, and CTL groups, IL-6 in DH and D groups was significantly lower than the CTL group. The serum level of TGF-β and IL-4 cytokines did not show any significant differences across the four groups. Serum levels of IL-6 were also significantly lower in untreated patients in D group than controls and in DH when compared with H groups. CONCLUSION In conclusion, it appears that the proinflammatory and anti-inflammatory cytokines either play a significant role in the pathogenesis of hypertension and DM or serve as markers for these pathologies. Accordingly, increased serum levels of IFN-γ may participate in the pathogenesis of hypertension in the diabetic patients and decreased IL-6 is associated with type 2 DM.
Collapse
Affiliation(s)
- Gholamreza Asadikaram
- Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran.,Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Ram
- Department of Biochemistry, Taft Payam Noor University, Yazd, Iran
| | - Alireza Izadi
- Department of Medical Mycology and Parasitology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mahmood Sheikh Fathollahi
- Department of Epidemiology and Biostatistics, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
| | - Mohammad Hadi Nematollahi
- Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Hamid Najafipour
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Bidollah Shahoozehi
- Department of Biochemistry, Afzalipur Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Mohammad Masoumi
- Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran
| | - Nader Shahrokhi
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Kazemi Arababadi
- Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.,Department of Immunology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Kerman, Iran
| |
Collapse
|
|
36
|
Fatahi S, Kord Varkaneh H, Teymouri A, Azadbakht L. Beneficiary effect of a-lipoic acid supplementation on C-reactive protein level among adults. ACTA ACUST UNITED AC 2018. [DOI: 10.1108/nfs-03-2018-0082] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose
Clinical evidence has suggested that alpha-lipoic acid (ALA), a potent antioxidant, seems to have some effects on inflammatory process. However, these results are equivocal. The purpose of this paper is to investigate the nature of association between ALA and serum C-reactive protein (CRP) level by pooling the results from clinical trial studies.
Design/methodology/approach
Relevant studies were identified by systematic literature search of PubMed/MEDLINE, Scopus, Web of Sciences and Cochrane library up to September 2016 for randomized controlled trials (RCTs) evaluating the impact of ALA supplementation on CRP. The pooled data were summarized as weighted mean difference (WMD) and 95 per cent confidence interval (CI). Effect sizes of eligible studies were pooled using random- or fixed-effects (the DerSimonian–Laird estimator) depending on the results of heterogeneity tests.
Findings
Of 212 papers, 15 were eligible RCTs according to inclusion criteria. The selected studies comprised 1,408 cases and 457 controls. The dose of ALA supplement ranged from 300 to 1,200 mg, and the duration of follow-up was from 1 to 48 weeks. ALA supplementation significantly reduced the levels of circulating CRP (WMD: −0.088, 95 per cent CI: −0.131, −0.045, p < 0.001) with significant heterogeneity (I2 = 73.4 per cent, p < 0.001). Populations with age younger than 50 years (PMD: −0.060 mg/dl), receiving doses less than 600 mg/day (PMD: −0.057 mg/dl), having cardiovascular disease (PMD: −0.105 mg/dl), hemodialysis (PMD: −0.209 mg/dl), diabetes (PMD: −0.021 mg/dl) and otherwise healthy subjects (PMD: −0.045 mg/dl) were sources of heterogeneity.
Originality/Value
This meta-analysis of RCTs suggests that ALA supplementation seems to significantly reduce circulating CRP level.
Collapse
|
|
37
|
Hu M, Yu Z, Luo D, Zhang H, Li J, Liang F, Chen R. Association between -174G>C polymorphism in the IL-6 promoter region and the risk of obesity: A meta-analysis. Medicine (Baltimore) 2018; 97:e11773. [PMID: 30113463 PMCID: PMC6112883 DOI: 10.1097/md.0000000000011773] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Many researchers have suggested that the -174G>C polymorphism in the interleukin-6 (IL-6) promoter region contributes to the risk of obesity; however, this hypothesis is still inconclusive. Therefore, we conducted a meta-analysis to combine the data from several studies to arrive at a conclusion regarding the association between -174G>C polymorphism and the risk of obesity. METHODS The PubMed and Embase databases were searched up to February 20, 2018. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a random-effects model. Subgroup analysis and sensitivity were also performed. RESULTS Ten eligible studies involving 7210 cases were performed to identify the association strength. The association strength was measured by the ORs and 95% CIs. By pooling the eligible studies, we found a significant association between the -174G>C polymorphism and obesity risk (C vs G: OR = 1.37; 95% CI, 1.08-1.74; Pheterogeneity < .01). Overall, individuals with the variant CC (OR = 1.58; 95% CI, 1.09-2.28; Pheterogeneity < 0.01) and GC/CC (OR = 1.61; 95% CI, 1.13-2.29; Pheterogeneity < .01) were associated with a significantly increased risk of obesity. CONCLUSION The meta-analysis results suggested that the polymorphism -174G>C in the IL-6 promoter region was associated with a significantly increased risk of obesity.
Collapse
Affiliation(s)
- Man Hu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College
| | - Zhaomin Yu
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College
| | - Dan Luo
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College
| | - Haiming Zhang
- Department of Oncology, Integrated Traditional Chinese and Western Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei
| | - Jinxiao Li
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College
| | - Fengxia Liang
- Department of Acupuncture and Moxibustion, Hubei University of Chinese Medicine
| | - Rui Chen
- Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| |
Collapse
|
|
38
|
Kang J, Lee CN, Li HY, Hsu KH, Wang SH, Lin SY. Association of Interleukin-10 Methylation Levels With Gestational Diabetes in a Taiwanese Population. Front Genet 2018; 9:222. [PMID: 29988451 PMCID: PMC6024195 DOI: 10.3389/fgene.2018.00222] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 06/04/2018] [Indexed: 11/13/2022] Open
Abstract
Objective: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset during pregnancy, which is also associated with future metabolic diseases in both patients and their offspring. The mechanisms underlying this condition remain largely unknown and may be partly related to epigenetics. The aim of this study was to compare the methylation levels of the cytokine interleukin-10 (IL-10) in pregnant women and their fetuses under both hyperglycemic and euglycemic environments, as those levels may be a clue to the epigenetic mechanisms underlying pathogenesis of GDM. Methods: We analyzed the methylation levels of the IL-10 gene in maternal blood, cord blood, and placental tissue in both a GDM group (n = 8) and a control group (n = 24) using a LightCycler LC480 (Roche, Rotkreuz, Switzerland). IL-10 concentrations in maternal blood and THP-1 cells were measured by enzyme-linked immunosorbent assay (ELISA) using BD OptEIA Human IL-10 ELISA kits (BD Biosciences Pharmingen, San Diego, CA, United States). Results: The maternal blood IL-10 methylation levels in the GDM group and the control group were 0.23 ± 0.04 and 0.26 ± 0.04, respectively (p = 0.03), but there were no significant differences between the levels of the two groups in the cord blood or placental tissue. Increased IL-10 plasma concentrations were discovered under hyperglycemic environments and were confirmed via the THP-1 cell line. Conclusion: Hypomethylation of maternal blood and increased plasma IL-10 concentrations before birth were found in the GDM group.
Collapse
Affiliation(s)
- Jessica Kang
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Nan Lee
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Yuan Li
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kai-Han Hsu
- Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shu-Huei Wang
- Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Shin-Yu Lin
- Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
39
|
Hameed I, Masoodi SR, Malik PA, Mir SA, Ghazanfar K, Ganai BA. Genetic variations in key inflammatory cytokines exacerbates the risk of diabetic nephropathy by influencing the gene expression. Gene 2018; 661:51-59. [PMID: 29605608 DOI: 10.1016/j.gene.2018.03.095] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2017] [Revised: 03/24/2018] [Accepted: 03/28/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND Diabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. METHODS We screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-β) in 1326 unrelated subjects comprising of healthy controls (n = 464), type 2 diabetics with nephropathy (DN, n = 448) and type 2 diabetes without nephropathy (T2D, n = 414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). RESULTS Individual SNP analysis showed highest association of IL-1β rs16944-TT genotype (OR = 3.51, 95%CI = 2.36-5.21, P = 0.001) and TNF-α rs1800629-AA genotype (OR = 2.75, 95% CI = 1.64-4.59, P = 0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (OR = 4.25, 95%CI = 3.3-14.20, P = 0.0016) and GACGACCTT (OR = 21.3, 95%CI = 15.1-28.33, P = 0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-fold = 4.43 ± 1.11) in DN. TNF-α, IL-6 and IL-1β transcript levels were significantly modulated by promoter region SNPs. CONCLUSIONS The present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1β gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects.
Collapse
Affiliation(s)
- Iqra Hameed
- Department of Biochemistry, University of Kashmir, Hazratbal Srinagar, India; Department of Biochemistry and Molecular Biology, GK Medical Trust, Srinagar, India
| | - Shariq R Masoodi
- Department of Endocrinology and Metabolism, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India; Department of Endocrinology, Diabetes & Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Perveez A Malik
- Department of Minimal Access Surgery, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
| | - Shahnaz A Mir
- Department of Endocrinology, Government Medical College and Associated Hospital, Srinagar, India
| | | | - Bashir A Ganai
- Center for Research and Development, University of Kashmir, Srinagar, India.
| |
Collapse
|
|
40
|
Qiao YC, Wang M, Pan YH, Zhang XX, Tian F, Chen YL, Zhao HL. The relationship between ACE/AGT gene polymorphisms and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes. J Renin Angiotensin Aldosterone Syst 2018; 19:1470320317752955. [PMID: 29378484 PMCID: PMC5843891 DOI: 10.1177/1470320317752955] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Aims: This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes. Methods: We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate. Results: Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ2 = 150.713, p < 0.001). The DR cases and DNR individuals did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons. Conclusions: The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association.
Collapse
Affiliation(s)
- Yong-Chao Qiao
- 1 Department of Immunology, Xiangya School of Medicine, Central South University, China
| | - Min Wang
- 2 Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, China.,3 Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, China
| | - Yan-Hong Pan
- 2 Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, China
| | - Xiao-Xi Zhang
- 2 Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, China.,3 Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, China
| | - Fang Tian
- 1 Department of Immunology, Xiangya School of Medicine, Central South University, China
| | - Yin-Ling Chen
- 2 Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, China.,3 Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, China
| | - Hai-Lu Zhao
- 1 Department of Immunology, Xiangya School of Medicine, Central South University, China.,2 Center for Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, China.,3 Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, China
| |
Collapse
|
|
41
|
Yu Y, Chen Y, Wang FL, Sun J, Li HJ, Liu JM. Cytokines Interleukin 4 (IL-4) and Interleukin 10 (IL-10) Gene Polymorphisms as Potential Host Susceptibility Factors in Virus-Induced Encephalitis. Med Sci Monit 2017; 23:4541-4548. [PMID: 28935853 PMCID: PMC5683680 DOI: 10.12659/msm.904364] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background This study aimed to analyze and explore the relationship between the cytokines IL-4 and IL-10 in relation to gene polymorphism and their respective effects on the susceptibility to virus-induced encephalitis. Material/Methods From January 2012 to June 2013, 112 patients with virus-induced encephalitis (the case group and 109 healthy individuals (the control group) were recruited for the purposes of this study. The functional variations that IL-4 and IL-10 genes exhibit were detected through the use of a function analysis and selection tool for single-nucleotide polymorphisms (FASTSNP). The genotypes of IL-4 were rs2227283 and IL-4 rs2227288, and the genotypes of IL-10 were rs1800871 and IL-10 rs1800872. These genotypes were respectively assessed using direct sequencing. Results IL-4 rs2227283 and IL-10 rs1800871 have no correlation in with risk of virus-induced encephalitis (both P>0.05) GA and AA genotypes were related to IL-4 rs2227288 and GT, while TT and GT + TT genotypes were related to IL-10 rs1800872. These were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). However, the duration of fever, white blood cell (WBC) count, C-reactive protein (CRP), neutrophils, and lymphocytes and monocytes of virus-induced encephalitis patients with IL-4 rs2227288 and IL-10 rs1800872 all displayed significant differences (all P<0.05). Frequencies of GAGT and CAGT haplotypes were evaluated and deemed to be of statistical significance and subsequently were highlighted as being risk factors in virus-induced encephalitis (all P<0.05). Conclusions IL-4 rs2227288 and IL-10 rs1800872 may contribute to an increased risk for virus-induced encephalitis. Through use of direct sequencing, we showed that genotypes of IL-4 rs2227288 and IL-10 rs1800872 may have particular host susceptibility to virus-induced encephalitis.
Collapse
Affiliation(s)
- Ying Yu
- Department of Infectious Diseases, Taizhou Municipal Hospital, Taizhou, Zhejiang, China (mainland)
| | - Ying Chen
- Department of Neurology, Taizhou Municipal Hospital, Taizhou, Zhejiang, China (mainland)
| | - Feng-Ling Wang
- Department of Infectious Diseases, Taizhou Municipal Hospital, Taizhou, Zhejiang, China (mainland)
| | - Jing Sun
- Department of Neurology, The Second Hospital Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| | - Hai-Jun Li
- Department of Neurology, Taizhou Municipal Hospital, Taizhou, Zhejiang, China (mainland)
| | - Jia-Ming Liu
- Wenzhou Medical University, Wenzhou, Zhejiang, China (mainland)
| |
Collapse
|
|
42
|
Song C, Leng J, Wang L, Li W, Zhang S, Wang W, Liu P, Zhang J, Xie B, Li W, Chan JCN, Yang X. ABO blood types and postpartum depression among Chinese women: A prospective cohort study in Tianjin, China. Women Health 2017; 58:685-698. [DOI: 10.1080/03630242.2017.1333077] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Chunhua Song
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Junhong Leng
- Tianjin Women and Children’s Health Center, Tianjin, China
| | - Leishen Wang
- Tianjin Women and Children’s Health Center, Tianjin, China
| | - Wei Li
- Tianjin Women and Children’s Health Center, Tianjin, China
| | - Shuang Zhang
- Tianjin Women and Children’s Health Center, Tianjin, China
| | - Wei Wang
- Tianjin Hedong Women and Children’s Health Center, Tianjin, China
| | - Pingying Liu
- Tianjin Hebei Women and Children’s Health and Family Planning Center, Tianjin, China
| | - Jing Zhang
- Tianjin Hexi Women and Children’s Health and Family Planning Center, Tianjin, China
| | - Bin Xie
- Tianjin Hongqiao Women and Children’s Health and Family Planning Center, Tianjin, China
| | - Weidong Li
- Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Juliana C. N. Chan
- Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and The Chinese University of Hong Kong-Prince of Wales Hospital-International Diabetes Federation Centre of Education, Hong Kong SAR, China
| | - Xilin Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
| |
Collapse
|
|
43
|
Qiao YC, Chen YL, Pan YH, Tian F, Xu Y, Zhang XX, Zhao HL. The change of serum tumor necrosis factor alpha in patients with type 1 diabetes mellitus: A systematic review and meta-analysis. PLoS One 2017; 12:e0176157. [PMID: 28426801 PMCID: PMC5398633 DOI: 10.1371/journal.pone.0176157] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2016] [Accepted: 04/06/2017] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE The aim of this study was used meta-analysis to investigate changes of serum tumor necrosis factor-alpha (TNF-α) in patients with type 1 diabetes mellitus (T1DM). METHODS Relevant literatures were identified from PubMed, Cochrane Library, CNKI, WanFang and Chinese-Cqvip databases (published from January 1, 1999 to September 30, 2016). Eligible reports were included for pooled analysis of serum TNF-α level and subgroup analysis was performed in relation with age, disease duration and ethnicity. RESULTS A total of 23 articles (1631 T1DM cases, 1429 healthy controls) were included for this meta-analysis. Compared with the controls, the patients had significantly increased serum TNF-α level (P < 0.001). Similar results were also found among all subgroup analysis of different age, disease duration and ethnicity (with the exception of Asian) (all P < 0.05). Regression analysis indicated that age (P = 0.680), disease duration (P = 0.957), and ethnicity (P = 0.526) of patients were not significant impact factors for the high heterogeneity. The results were stable according to the sensitivity analysis and no publication bias existed in this meta-analysis. CONCLUSIONS Serum TNF-α level in T1DM patients has significantly elevated among all age, disease duration and ethnicity groups.
Collapse
Affiliation(s)
- Yong-chao Qiao
- Center of Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin, China
- Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yin-ling Chen
- Center of Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin, China
- Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, Guilin, China
| | - Yan-hong Pan
- Center of Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin, China
- Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, Guilin, China
| | - Fang Tian
- Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Yan Xu
- Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Xiao-xi Zhang
- Center of Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin, China
- Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, Guilin, China
| | - Hai-lu Zhao
- Center of Diabetic Systems Medicine, Guangxi Key Laboratory of Excellence, Guilin Medical University, Guilin, China
- Department of Immunology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China
- Department of Immunology, Faculty of Basic Medicine, Guilin Medical University, Guilin, China
| |
Collapse
|
|
44
|
The relationship of Interleukin-6 -174 G>C gene polymorphism in type 2 diabetic patients with and without diabetic foot ulcers in Turkish population. Foot (Edinb) 2017; 30:27-31. [PMID: 28257947 DOI: 10.1016/j.foot.2017.02.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Revised: 01/04/2017] [Accepted: 02/07/2017] [Indexed: 02/04/2023]
Abstract
OBJECTIVE We aims investigate Turkish type 2 diabetic patients with/without diabetic foot ulcers and healthy group and examined the contribution of Interleukin (IL)-6 -174 G>C gene polymorphism to the development of diabetic foot ulcers. DESIGN AND PATIENTS The Interleukin (IL)-6 -174 G>C genotypes were determined prospectively in 50 patients with diabetic foot ulcers and 35 without diabetic foot ulcers and a control group of 119 healthy individuals. Genotyping of the Interleukin (IL)-6 -174 G>C gene polymorphisms for all individuals was performed by PCR-RFLP method. RESULTS The genotype IL6 distribution did differ between the control group (CC 13.3%, GC 66.7%, GG 20%) and type 2 diabetic patients (CC 2.4%, GC 47.1%, GG 50.6%) (P<0.001). The genotype IL6 distribution did not differ between type 2 diabetic patients group (CC 0%, GC 45.7%, GG 54.3%) and diabetic foot ulcers (CC 4%, GC 48%, 48%) (P>0.05). The frequency of the polymorphic G allele in between the control group and type 2 diabetic patients was no similar for the groups (58.4% and 74.1%, respectively) (p<0.05). The frequency of the polymorphic G allele in between the type 2 diabetic patients and diabetic foot ulcers was similar for the groups (77.1% and 72%, respectively) (p>0.05). CONCLUSION The gene polymorphism of Interleukin-6 -174 G>C and G allele are an risk factor for diabetes, but gene polymorphism of Interleukin-6 -174 G>C is not an independent risk factor for diabetic foot. Genetic factors in the pathogenesis of diabetic foot may also show any changes in different populations.
Collapse
|
|
45
|
Rodrigues KF, Pietrani NT, Bosco AA, Campos FMF, Sandrim VC, Gomes KB. IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2017; 61:438-446. [PMID: 28225860 PMCID: PMC10522244 DOI: 10.1590/2359-3997000000254] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Accepted: 11/25/2016] [Indexed: 11/22/2022]
Abstract
OBJECTIVE This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. SUBJECTS AND METHODS One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. RESULTS IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. CONCLUSIONS These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.
Collapse
Affiliation(s)
- Kathryna Fontana Rodrigues
- Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteMGBrasilInstituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brasil
| | - Nathalia Teixeira Pietrani
- Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteMGBrasilInstituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brasil
| | - Adriana Aparecida Bosco
- Instituto de Ensino e PesquisaSanta Casa de Belo HorizonteBelo HorizonteMGBrasilInstituto de Ensino e Pesquisa, Santa Casa de Belo Horizonte, Belo Horizonte, MG, Brasil
| | | | - Valéria Cristina Sandrim
- Instituto de BiociênciasUniversidade Estadual Paulista Júlio de Mesquita FilhoBotucatuSPBrasilInstituto de Biociências, Universidade Estadual Paulista Júlio de Mesquita Filho (Unesp), Botucatu, SP, Brasil
| | - Karina Braga Gomes
- Faculdade de FarmáciaUFMGBelo HorizonteMGBrasilFaculdade de Farmácia, UFMG, Belo Horizonte, MG, Brasil
| |
Collapse
|
|
46
|
Fan L, Feng Y, Chen GC, Qin LQ, Fu CL, Chen LH. Effects of coenzyme Q10 supplementation on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2017; 119:128-136. [PMID: 28179205 DOI: 10.1016/j.phrs.2017.01.032] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 01/20/2017] [Accepted: 01/27/2017] [Indexed: 12/17/2022]
Abstract
The aims of this meta-analysis were to evaluate the effects of coenzyme Q10 (CoQ10) supplementation on inflammatory mediators including C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by analyzing published randomized controlled trials (RCTs). A systematic search in PubMed, Cochrane Library and Clinicaltrials.gov was performed to identify eligible RCTs. Data synthesis was performed using a random- or a fixed-effects model depending on the results of heterogeneity tests, and pooled data were displayed as weighed mean difference (WMD) and 95% confidence interval (CI). Seventeen RCTs were selected for the meta-analysis. CoQ10 supplementation significantly reduced the levels of circulating CRP (WMD: -0.35mg/L, 95% CI: -0.64 to -0.05, P=0.022), IL-6 (WMD: -1.61pg/mL, 95% CI: -2.64 to -0.58, P=0.002) and TNF-α (WMD: -0.49pg/mL, 95% CI: -0.93 to -0.06, P=0.027). The results of meta-regression showed that the changes of CRP were independent of baseline CRP, treatment duration, dosage, and patients characteristics. In the meta-regression analyses, a higher baseline IL-6 level was significantly associated with greater effects of CoQ10 on IL-6 levels (P for interaction=0.006). In conclusion, this meta-analysis of RCTs suggests significant lowering effects of CoQ10 on CRP, IL-6 and TNF-α. However, results should be interpreted with caution because of the evidence of heterogeneity and limited number of studies.
Collapse
Affiliation(s)
- Li Fan
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
| | - Yu Feng
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China; The Second Affiliated Hospital of Soochow University,1055 Sanxiang Road, Suzhou 215004, China.
| | - Guo-Chong Chen
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
| | - Li-Qiang Qin
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
| | - Chun-Ling Fu
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
| | - Li-Hua Chen
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Department of Nutrition and Food Hygiene, School of Public Health, Soochow University, 199 Renai Road, Dushu Lake Higher Education Town, Suzhou 215123, China.
| |
Collapse
|
|
47
|
Winer DA, Winer S, Dranse HJ, Lam TKT. Immunologic impact of the intestine in metabolic disease. J Clin Invest 2017; 127:33-42. [PMID: 28045403 DOI: 10.1172/jci88879] [Citation(s) in RCA: 57] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Obesity and diabetes are associated with increased chronic low-grade inflammation and elevated plasma glucose levels. Although inflammation in the fat and liver are established features of obesity-associated insulin resistance, the intestine is emerging as a new site for immunologic changes that affect whole-body metabolism. Specifically, microbial and dietary factors incurred by diet-induced obesity influence underlying innate and adaptive responses of the intestinal immune system. These responses affect the maintenance of the intestinal barrier, systemic inflammation, and glucose metabolism. In this Review we propose that an understanding of the changes to the intestinal immune system, and how these changes influence systemic immunity and glucose metabolism in a whole-body integrative and a neuronal-dependent network, will unveil novel intestinal pathologic and therapeutic targets for diabetes and obesity.
Collapse
|
|
48
|
Zhuanping Z, Rifang L, Qing C, Sidong C. Association between interleukin 6, 10 gene polymorphisms and risk of type 2 diabetes mellitus in a Chinese population. Meta Gene 2016. [DOI: 10.1016/j.mgene.2016.09.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
|
|
49
|
Singh S, Usman K, Banerjee M. Pharmacogenetic studies update in type 2 diabetes mellitus. World J Diabetes 2016; 7:302-315. [PMID: 27555891 PMCID: PMC4980637 DOI: 10.4239/wjd.v7.i15.302] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Revised: 05/30/2016] [Accepted: 06/29/2016] [Indexed: 02/05/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs (OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters (SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.
Collapse
|
|
50
|
Mărginean C, Mărginean CO, Bănescu C, Meliţ L, Tripon F, Iancu M. Impact of demographic, genetic, and bioimpedance factors on gestational weight gain and birth weight in a Romanian population: A cross-sectional study in mothers and their newborns: the Monebo study (STROBE-compliant article). Medicine (Baltimore) 2016; 95:e4098. [PMID: 27399105 PMCID: PMC5058834 DOI: 10.1097/md.0000000000004098] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
The present study had 2 objectives, first, to investigate possible relationships between increased gestational weight gain and demographic, clinical, paraclinical, genetic, and bioimpedance (BIA) characteristics of Romanian mothers, and second, to identify the influence of predictors (maternal and newborns characteristics) on our outcome birth weight (BW).We performed a cross-sectional study on 309 mothers and 309 newborns from Romania, divided into 2 groups: Group I-141 mothers with high gestational weight gain (GWG) and Group II-168 mothers with normal GWG, that is, control group.The groups were evaluated regarding demographic, anthropometric (body mass index [BMI], middle upper arm circumference, tricipital skinfold thickness, weight, height [H]), clinical, paraclinical, genetic (interleukin 6 [IL-6]: IL-6 -174G>C and IL-6 -572C>G gene polymorphisms), and BIA parameters.We noticed that fat mass (FM), muscle mass (MM), bone mass (BM), total body water (TBW), basal metabolism rate (BMR) and metabolic age (P < 0.001), anthropometric parameters (middle upper arm circumference, tricipital skinfold thickness; P < 0.001/P = 0.001) and hypertension (odds ratio = 4.65, 95% confidence interval: 1.27-17.03) were higher in mothers with high GWG. BW was positively correlated with mothers' FM (P < 0.001), TBW (P = 0.001), BMR (P = 0.02), while smoking was negatively correlated with BW (P = 0.04). Variant genotype (GG+GC) of the IL-6 -572C>G polymorphism was higher in the control group (P = 0.042).We observed that high GWG may be an important predictor factor for the afterward BW, being positively correlated with FM, TBW, BMR, metabolic age of the mothers, and negatively with the mother's smoking status. Variant genotype (GG+GC) of the IL-6 -572C>G gene polymorphism is a protector factor against obesity in mothers. All the variables considered explained 14.50% of the outcome variance.
Collapse
Affiliation(s)
| | | | - Claudia Bănescu
- Department of Genetics, University of Medicine and Pharmacy, Tîrgu Mureţ
- Correspondence: Claudia Bănescu, Department of Medical Genetics, University of Medicine and Pharmacy Tirgu Mures, 38 Gh Marinescu St, 540139, Tirgu Mures, Romania (e-mail: )
| | | | - Florin Tripon
- Department of Genetics, University of Medicine and Pharmacy, Tîrgu Mureţ
| | - Mihaela Iancu
- Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy, Cluj Napoca, Romania
| |
Collapse
|