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Muntean M, Mărginean C, Bernad ES, Bănescu C, Nyulas V, Muntean IE, Săsăran V. Adiponectin C1Q and Collagen Domain Containing rs266729, Cyclin-Dependent Kinase Inhibitor 2A and 2B rs10811661, and Signal Sequence Receptor Subunit 1 rs9505118 Polymorphisms and Their Association with Gestational Diabetes Mellitus: A Case-Control Study in a Romanian Population. Int J Mol Sci 2025; 26:1654. [PMID: 40004118 PMCID: PMC11855124 DOI: 10.3390/ijms26041654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Revised: 02/08/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) are public health concerns worldwide. These two diseases share the same pathophysiological and genetic similarities. This study aimed to investigate the T2DM known single nucleotide polymorphisms (SNPs) of the adiponectin C1Q and collagen domain containing (ADIPOQ), cyclin-dependent kinase inhibitor 2A and 2B (CDKN2A/2B), and signal sequence receptor subunit 1 (SSR1) genes in a cohort of Romanian GDM pregnant women and perinatal outcomes. DNA was isolated from the peripheral blood of 213 pregnant women with (n = 71) or without (n = 142) GDM. Afterward, ADIPOQ (rs266729), CDKN2A/2B (rs10811661), and SSR1 (rs9505118) gene polymorphisms were genotyped using TaqMan Real-Time PCR analysis. Women with GDM had a higher pre-pregnancy body mass index (BMI) (p < 0.0001), higher BMI (p < 0.0001), higher insulin resistance homeostatic model assessment (IR-HOMA) (p = 0.0002), higher insulin levels (p = 0.003), and lower adiponectin levels (p = 0.004) at birth compared to pregnant women with normoglycemia. GDM pregnant women had gestational hypertension (GH) more frequently during pregnancy (p < 0.0001), perineal lacerations more frequently during vaginal birth (p = 0.03), and more macrosomic newborns (p < 0.0001) than pregnant women from the control group. We did not find an association under any model (allelic, genotypic, dominant, or recessive) of ADIPOQ rs266729, CDKN2A/2B rs10811661, and SSR1 rs9505118 polymorphisms and GDM. In correlation analysis, we found a weak positive correlation (r = 0.24) between the dominant model GG + CG vs. CC of rs266729 and labor induction failure. In the dominant model TT vs. CC + CT of rs10811661, we found a weak negative correlation between this model and perineal lacerations. Our results suggest that the ADIPOQ rs266729, the CDKN2A/2B rs10811661, and the SSR1 rs9505118 gene polymorphisms are not associated with GDM in a cohort of Romanian pregnant women.
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Affiliation(s)
- Mihai Muntean
- Department of Obstetrics and Gynecology 2, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania; (M.M.); (V.S.)
| | - Claudiu Mărginean
- Department of Obstetrics and Gynecology 2, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania; (M.M.); (V.S.)
| | - Elena Silvia Bernad
- Department of Obstetrics and Gynecology, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania;
- Clinic of Obstetrics and Gynecology, “Pius Brinzeu” County Clinical Emergency Hospital, 300723 Timisoara, Romania
- Center for Laparoscopy, Laparoscopic Surgery and In Vitro Fertilization, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Claudia Bănescu
- Genetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania;
| | - Victoria Nyulas
- Departament of Informatics and Medical Biostatistics, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania;
| | | | - Vladut Săsăran
- Department of Obstetrics and Gynecology 2, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania; (M.M.); (V.S.)
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Suthon S, Tangjittipokin W. Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus. Int J Mol Sci 2024; 25:2039. [PMID: 38396716 PMCID: PMC10888615 DOI: 10.3390/ijms25042039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 02/03/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Gestational diabetes mellitus (GDM) is a significant pregnancy complication linked to perinatal complications and an elevated risk of future metabolic disorders for both mothers and their children. GDM is diagnosed when women without prior diabetes develop chronic hyperglycemia due to β-cell dysfunction during gestation. Global research focuses on the association between GDM and single nucleotide polymorphisms (SNPs) and aims to enhance our understanding of GDM's pathogenesis, predict its risk, and guide patient management. This review offers a summary of various SNPs linked to a heightened risk of GDM and explores their biological mechanisms within the tissues implicated in the development of the condition.
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Affiliation(s)
- Sarocha Suthon
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
- Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
- Siriraj Center of Research Excellence Management, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
| | - Watip Tangjittipokin
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand;
- Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
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Lizárraga D, Gómez-Gil B, García-Gasca T, Ávalos-Soriano A, Casarini L, Salazar-Oroz A, García-Gasca A. Gestational diabetes mellitus: genetic factors, epigenetic alterations, and microbial composition. Acta Diabetol 2024; 61:1-17. [PMID: 37660305 DOI: 10.1007/s00592-023-02176-y] [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: 06/07/2023] [Accepted: 08/18/2023] [Indexed: 09/05/2023]
Abstract
Gestational diabetes mellitus (GDM) is a common metabolic disorder, usually diagnosed during the third trimester of pregnancy that usually disappears after delivery. In GDM, the excess of glucose, fatty acids, and amino acids results in foetuses large for gestational age. Hyperglycaemia and insulin resistance accelerate the metabolism, raising the oxygen demand, and creating chronic hypoxia and inflammation. Women who experienced GDM and their offspring are at risk of developing type-2 diabetes, obesity, and other metabolic or cardiovascular conditions later in life. Genetic factors may predispose the development of GDM; however, they do not account for all GDM cases; lifestyle and diet also play important roles in GDM development by modulating epigenetic signatures and the body's microbial composition; therefore, this is a condition with a complex, multifactorial aetiology. In this context, we revised published reports describing GDM-associated single-nucleotide polymorphisms (SNPs), DNA methylation and microRNA expression in different tissues (such as placenta, umbilical cord, adipose tissue, and peripheral blood), and microbial composition in the gut, oral cavity, and vagina from pregnant women with GDM, as well as the bacterial composition of the offspring. Altogether, these reports indicate that a number of SNPs are associated to GDM phenotypes and may predispose the development of the disease. However, extrinsic factors (lifestyle, nutrition) modulate, through epigenetic mechanisms, the risk of developing the disease, and some association exists between the microbial composition with GDM in an organ-specific manner. Genes, epigenetic signatures, and microbiota could be transferred to the offspring, increasing the possibility of developing chronic degenerative conditions through postnatal life.
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Affiliation(s)
- Dennise Lizárraga
- Laboratory of Molecular and Cell Biology, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico
| | - Bruno Gómez-Gil
- Laboratory of Microbial Genomics, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico
| | - Teresa García-Gasca
- Laboratory of Molecular and Cellular Biology, Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Avenida de las Ciencias s/n, 76230, Juriquilla, Querétaro, Mexico
| | - Anaguiven Ávalos-Soriano
- Laboratory of Molecular and Cell Biology, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico
| | - Livio Casarini
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy
| | - Azucena Salazar-Oroz
- Maternal-Fetal Department, Instituto Vidalia, Hospital Sharp Mazatlán, Avenida Rafael Buelna y Dr. Jesús Kumate s/n, 82126, Mazatlán, Sinaloa, Mexico
| | - Alejandra García-Gasca
- Laboratory of Molecular and Cell Biology, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico.
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Zhu M, Lv Y, Peng Y, Wu Y, Feng Y, Jia T, Xu S, Li S, Wang W, Tian J, Sun L. GCKR and ADIPOQ gene polymorphisms in women with gestational diabetes mellitus. Acta Diabetol 2023; 60:1709-1718. [PMID: 37524927 PMCID: PMC10587232 DOI: 10.1007/s00592-023-02165-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/18/2023] [Indexed: 08/02/2023]
Abstract
AIMS To investigate the associations of GCKR and ADIPOQ variants with the risk of gestational diabetes mellitus (GDM) in Chinese women. METHODS GCKR rs1260326, ADIPOQ rs266729, and rs1501299 were selected and genotyped in 519 GDM patients and 498 controls. Candidate SNPs were genotyped using multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods, and the association of these SNPs with GDM was analyzed. RESULTS We found that GCKR rs1260326 was significantly associated with an increased risk of GDM in the allele model, the codominant model (CC vs. TT), the dominant model, the recessive model, and the genotypic model distributions (p = 0.0029, p = 0.0022, p = 0.0402, p = 0.0038, and p = 0.0028, respectively). The rs1260326 polymorphism was shown to be associated with 1 h-OGTT level and gravidity in GDM patients (CC vs. TT: p = 0.0475 and p = 0.0220, respectively). Diastolic blood pressure (DBP) was significantly higher in the GDM patients with the rs266729 GG genotype compared to those with the CC or CG genotype (p = 0.0444 and p = 0.0339, respectively). The DBP of the GDM patients with the rs1501299 GT genotype was lower than that of those with the GG genotype (p = 0.0197). There was a weak linkage disequilibrium value between the GCKR and ADIPOQ SNPs. CONCLUSIONS The genes GCKR and ADIPOQ may be involved in the pathophysiology of GDM.
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Affiliation(s)
- Manning Zhu
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yaer Lv
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yanqing Peng
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yingnan Wu
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Yanan Feng
- Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
| | - Tianshuang Jia
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Songcheng Xu
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Songxue Li
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Wei Wang
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Jiawei Tian
- Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
| | - Litao Sun
- Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
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Fernandez LFA, Pineda-Cortel MRB. ADIPOQ gene (T45G and G276T) single nucleotide polymorphisms and their association with gestational diabetes mellitus in a Filipino population. BMC Endocr Disord 2023; 23:248. [PMID: 37953238 PMCID: PMC10641948 DOI: 10.1186/s12902-023-01479-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 10/06/2023] [Indexed: 11/14/2023] Open
Abstract
Several studies have associated the presence of ADIPOQ gene polymorphisms with insulin resistance, adiponectin levels, and metabolic diseases such as diabetes, although with varying degrees of correlation depending on ethnicity. Here we aim to identify individual's susceptibility to gestational diabetes mellitus (GDM) in the presence of T45G and G276T single nucleotide polymorphisms (SNPs) within the ADIPOQ gene among Filipino pregnant women. A total of 285 pregnant women (95 GDM cases and 190 controls) were included in this study. Two ADIPOQ gene polymorphisms were genotyped using TaqMan assay. Results of SNP genotyping showed no significant differences in the frequencies of TT, TG and GG genotypes of T45G SNP between the GDM and control group [p = 1.0000, 0.6179, 0.5797; OR (95%CI) = 1.030 (0.582-1.874), 1.135 (0.683-1.828), 0.833 (0.481-1.420)]. Similarly, the frequencies of GG, GT, and TT genotypes of G276T SNP were comparable in both groups [p = 0.8002, 1.0000, 0.3466; OR (95%CI) = 1.090 (0.654-1.785), 1.022 (0.616-1.665), 0.433 (0.092-1.698)]. Moreover, although adiponectin levels were significantly decreased in GDM group (p = 0.0196) and have shown substantial negative correlations with FBS, 1-hour OGTT, 2-hour OGTT, and HOMA-IR (p < 0.05), they were not significantly different according to genotypes of T45G and G276T polymorphisms both in GDM and control group. Our results suggest that neither of the two ADIPOQ gene polymorphisms influence adiponectin levels and development of GDM in a Filipino population.
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Affiliation(s)
- Larah Francesca A Fernandez
- The Graduate School, University of Santo Tomas, Manila, Philippines
- Department of Medical Technology, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines
| | - Maria Ruth B Pineda-Cortel
- The Graduate School, University of Santo Tomas, Manila, Philippines.
- Research Center for the Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines.
- Department of Medical Technology, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines.
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Tan X, Chen H. Association between MTHFR gene C677T polymorphism and gestational diabetes mellitus in Chinese population: a meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1273218. [PMID: 37964957 PMCID: PMC10642752 DOI: 10.3389/fendo.2023.1273218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/13/2023] [Indexed: 11/16/2023] Open
Abstract
Background and purpose The relationship of the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with the incidence of gestational diabetes mellitus (GDM) in the Chinese population remains controversial. This study aimed to further clarify the effect of the MTHFR gene C677T polymorphism on GDM risk among Chinese pregnant women based on current evidence. Methods Several databases were searched up to July 29, 2023 for relevant case-control studies. The numbers of patients with and without the T allele of the MTHFR gene C677T polymorphism in the GDM and control groups were determined, and all statistical analyses were performed by RevMan 5.3 software and STATA 15.0 software. Trial sequential analysis (TSA) was performed by TSA version 0.9 beta software to determine the required information size. Results A total of 17 case-control studies involving 12345 Chinese participants were included. The pooled results demonstrated that the T allele of the MTHFR gene C677T polymorphism was significantly associated with an increased risk of GDM, which was manifested by the five gene models of the MTHFR C677T polymorphism [T vs. C: odds ratio (OR)=1.59, P=0.03; TT vs. CC: OR=2.24, P<0.001; TC vs. CC: OR=1.28, P=0.05; (TT+TC) vs. CC: OR=1.55, P=0.003; TT vs. (TC+CC): OR=1.89, P<0.001]. Subgroup analysis based on the regions indicated that the significant relationship between the T allele of the MTHFR gene C677T polymorphism and an increased risk of GDM was detected only among the southern population [T vs. C: OR=1.62, P=0.09; TT vs. CC: OR=2.22, P=0.004; TC vs. CC: OR=1.17, P=0.28; (TT+TC) vs. CC: OR=1.43, P=0.03; TT vs. (TC+CC): OR=1.97, P=0.006]. TSA plots showed that the information sizes for the association between the MTHFR gene C677T polymorphism and GDM risk were sufficient in the homozygote (TT vs. CC) and recessive (TT vs. TC+CC) models. Conclusion The MTHFR gene C677T polymorphism is closely related to susceptibility to GDM in the southern Chinese population, and the C-T mutation serves as an important genetic risk factor for GDM. More well-designed large case-control studies are needed to further confirm the above findings.
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Affiliation(s)
| | - Hongqin Chen
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) of Ministry of Education, Chengdu, Sichuan, China
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Alshammary AF, Ansar S, Farzan R, Alsobaie SF, Alageel AA, Al-Hakeem MM, Ali Khan I. Dissecting the Molecular Role of ADIPOQ SNPs in Saudi Women Diagnosed with Gestational Diabetes Mellitus. Biomedicines 2023; 11:biomedicines11051289. [PMID: 37238960 DOI: 10.3390/biomedicines11051289] [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: 03/24/2023] [Revised: 04/12/2023] [Accepted: 04/19/2023] [Indexed: 05/28/2023] Open
Abstract
The traditional definition of gestational diabetes mellitus (GDM) is the leading cause of carbohydrate intolerance in hyperglycemia of varying severity, with onset or initial detection during pregnancy. Previous studies have reported a relationship among obesity, adiponectin (ADIPOQ), and diabetes in Saudi Arabia. ADIPOQ is an adipokine that is produced and secreted by adipose tissue involved in the regulation of carbohydrate and fatty acid metabolism. This study investigated the molecular association between rs1501299, rs17846866, and rs2241766 single-nucleotide polymorphisms (SNPs) in ADIPOQ and GDM in Saudi Arabia. Patients with GDM and control patients were selected, and serum and molecular analyses were performed. Statistical analyses were performed on clinical data, Hardy Weinberg Equilibrium, genotype and allele frequencies, multiple logistic regression, ANOVA, haplotype, linkage disequilibrium, as well as MDR and GMDR analyses. The clinical data showed significant differences in various parameters between the GDM and non-GDM groups (p < 0.05). In GDM women with alleles, genotypes, and different genetic models, the rs1501299 and rs2241766 SNPs showed a strong association (p < 0.05). Multiple logistic regression analysis revealed a negative correlation (p > 0.05). This study concluded that rs1501299 and rs2241766 SNPs were strongly associated with GDM in women in Saudi Arabia.
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Affiliation(s)
- Amal F Alshammary
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
| | - Sabah Ansar
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
| | - Raed Farzan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
| | - Sarah F Alsobaie
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
| | - Arwa A Alageel
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
| | - Malak Mohammed Al-Hakeem
- Department of Obstetrics and Gynecology, College of Medicine, King Khalid University Hospital, Riyadh 11451, Saudi Arabia
| | - Imran Ali Khan
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia
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Kahmini FR, Gholijani N, Amirghofran Z, Daryabor G. Single nucleotide polymorphisms rs7799039 and rs2167270 in leptin gene and elevated serum levels of adiponectin predispose Iranians to Behçet's disease. Cytokine 2023; 162:156100. [PMID: 36470065 DOI: 10.1016/j.cyto.2022.156100] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Accepted: 11/21/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND Behçet's Disease (BD) is a chronic autoimmune disease with unknown etiology. Adipokines due to their roles in the regulation of immune responses might be important in the induction and progression of BD. SUBJECTS AND METHODS This case-control study included 340 patients with BD and 310 healthy controls. Single nucleotide polymorphisms (SNPs) in adiponectin (rs266729 and rs1501299) and leptin (rs7799039 and rs2167270) genes were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and serum levels of adipokines were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS A higher frequency of leptin rs7799039 GG, AG, and AG +GG genotypes and G allele was revealed in patients. Besides, patients had more leptin rs2167270 AG and AG +AA genotypes and A allele. Furthermore, rs2167270 AA genotype and A allele were more frequently seen in total and female patients who had genital aphthous. Patients had significantly more serum levels of adiponectin while those with genital aphthous had significantly more leptin levels. No significant association was observed between genotypes and alleles of adiponectin SNPs and BD. CONCLUSION Our findings indicated that leptin gene polymorphisms might predispose Iranian individuals to BD. Besides, elevated serum levels of adiponectin might facilitate BD pathogenesis.
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Affiliation(s)
- Fatemeh Rezaei Kahmini
- Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nasser Gholijani
- Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Amirghofran
- Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Gholamreza Daryabor
- Autoimmune Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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Tangjittipokin W, Narkdontri T, Teerawattanapong N, Thanatummatis B, Wardati F, Sunsaneevithayakul P, Boriboonhirunsarn D. The Variants in ADIPOQ are Associated with Maternal Circulating Adipokine Profile in Gestational Diabetes Mellitus. J Multidiscip Healthc 2023; 16:309-319. [PMID: 36748054 PMCID: PMC9899009 DOI: 10.2147/jmdh.s396238] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
Background Gestational diabetes mellitus (GDM) is the most common association with hyperglycemia and glucose intolerance during pregnancy. The adipokines play an important to control insulin secretion and glucose. This study aimed to investigate the association between maternal circulating adipokine levels and ADIPOQ gene polymorphism among pregnant women subjects with GDM and normal glucose tolerance (NGT). Methods Participants including 229 normal pregnant women and 197 GDM pregnant women were enrolled from 2015 to 2018 at Siriraj hospital. Serum adipokine levels including adiponectin, adipsin/factor D, NGAL/Lipocalin-2, total PAI-1, and resistin were measured by immunoassay. ADIPOQ variations were investigated including -11377C/G (rs266729), +45T/G (rs2241766), and +276G/T (rs1501299). Results Serum adiponectin concentration was also significantly decreased among the GDM who had aged less than 35 years old whereas adipsin levels were significantly lower among the GDM who had aged more than 35 years old. Also, adiponectin and total PAI-1 levels were significantly lower among the GDM who had a BMI of less than 30 kg/m2. The G allele frequency of ADIPOQ +45T/G was significantly different between GDM and controls (p = 0.03). ADIPOQ +45T/G was associated with an increased risk of GDM (odds ratio [OR]: 1.554; 95% confidence interval [CI]: 1.010-2.390; p=0.045). The -11377C/G was affected by the level of adiponectin (p = 0.04). The C allele of -11377C/G SNP declined serum adiponectin levels and may be a risk factor for GDM. Conclusion This study revealed that genetics play important roles in circulating adipokines among pregnant women. ADIPOQ polymorphisms had significant associations with adiponectin levels in GDM patients.
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Affiliation(s)
- Watip Tangjittipokin
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,Correspondence: Watip Tangjittipokin, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, Tel +66 2-419-6635, Fax +66 2-418-1636, Email
| | - Tassanee Narkdontri
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,Research Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nipaporn Teerawattanapong
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand,Research Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Benyapa Thanatummatis
- Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Fauchil Wardati
- Graduate Program in Immunology, Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Prasert Sunsaneevithayakul
- Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Dittakarn Boriboonhirunsarn
- Department of Obstetrics and Gynaecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Karami M, Mousavi SH, Rafiee M, Heidari R, Shahrokhi SZ. Biochemical and molecular biomarkers: unraveling their role in gestational diabetes mellitus. Diabetol Metab Syndr 2023; 15:5. [PMID: 36631877 PMCID: PMC9832639 DOI: 10.1186/s13098-023-00980-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 01/05/2023] [Indexed: 01/12/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is the most prevalent metabolic disorder during pregnancy, causing short- and long-term complications for both mother and baby. GDM is a multifactorial disease, and it may be affected by interactions between genetic, epigenetic, and environmental factors. However, the exact etiology is poorly understood. Despite the high prevalence of GDM, there is still debate regarding the optimal time for screening, the diagnostic threshold to apply, and the best strategies for treatment. Identifying effective strategies for therapeutic purposes as well as accurate biomarkers for prognostic and diagnostic purposes will reduce the GDM incidence and improve its management. In recent years, new biochemical and molecular biomarkers such as microRNAs, single-nucleotide polymorphisms, and DNA methylation have received great interest in the diagnosis of GDM. In this review, we discuss current and future diagnostic approaches for the detection of GDM and evaluate lifestyle and pharmacological strategies for GDM prevention.
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Affiliation(s)
- Masoumeh Karami
- Department of Biochemistry, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Seyyed Hossein Mousavi
- Department of Cardiology, School of Medicine, AJA University of Medical Sciences, Tehran, Iran
| | - Mohammad Rafiee
- Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Reza Heidari
- Medical Biotechnology Research Center, AJA University of Medical Sciences, Tehran, Iran
- Research Center for Cancer Screening and Epidemiology, AJA University of Medical Sciences, Tehran, Iran
| | - Seyedeh Zahra Shahrokhi
- Department of Biochemistry, School of Medicine, AJA University of Medical Sciences, Tehran, Iran.
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11
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Wang Y, Li L, Li P. Novel single nucleotide polymorphisms in gestational diabetes mellitus. Clin Chim Acta 2023; 538:60-64. [PMID: 36375523 DOI: 10.1016/j.cca.2022.11.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 11/06/2022] [Accepted: 11/07/2022] [Indexed: 11/13/2022]
Abstract
The association between gestational diabetes mellitus (GDM) and single nucleotide polymorphisms (SNPs) has attracted global research attention. Exploring SNPs can help us further understand the pathogenesis of GDM, predict the risk of GDM, and guide the management of GDM patients. In this review, we summarized the studies on the association between SNPs and GDM, focusing on novel SNPs published in the last 10 years. The SNPs identified to be associated with GDM included HMG20A (rs7178572), CDKAL1 (rs7756992, rs7754840, and rs7747752), ADIPOQ (rs266729 and rs17300539), MTHFR (rs1801133), IL10 (rs3021094), CDKN2B (rs1063192), and TRPM5 (rs35197079). However, the role of SNPs in the prediction, diagnosis, treatment, and prognosis of GDM, as a polygenic disease, needs to be further explored in multiple ethnic populations.
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Affiliation(s)
- Yuqi Wang
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China
| | - Ling Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China
| | - Ping Li
- Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.
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12
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Chen HH, Hsu HT, Liao MH, Teng MS. Effects of Sex and Obesity on LEP Variant and Leptin Level Associations in Intervertebral Disc Degeneration. Int J Mol Sci 2022; 23:ijms232012275. [PMID: 36293132 PMCID: PMC9603873 DOI: 10.3390/ijms232012275] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/03/2022] [Accepted: 10/11/2022] [Indexed: 12/04/2022] Open
Abstract
Intervertebral disc degeneration (IVDD), for which obesity and genetics are known risk factors, is a chronic process that alters the structure and function of the intervertebral discs (IVD). Circulating leptin is positively correlated with body weight and is often measured to elucidate the pathogenesis of IVD degeneration. In this study, we examined the associations of LEP single nucleotide polymorphisms (SNPs) genetic and environmental effects with IVDD. A total of 303 Taiwanese patients with IVDD (mean age, 58.6 ± 12.7 years) undergoing cervical discectomy for neck pain or lumbar discectomy for back pain were enrolled. Commercially available enzyme-linked immunosorbent assay (ELISA) kits measured the circulating plasma leptin levels. TaqMan SNP genotyping assays genotyped the LEP SNPs rs2167270 and rs7799039. Leptin levels were significantly increased in obese individuals (p < 0.001) and non-obese or obese women (p < 0.001). In the dominant model, recoded minor alleles of rs2167270 and rs7799039 were associated with higher leptin levels in all individuals (p = 0.011, p = 0.012). Further, the association between these LEP SNPs and leptin levels was significant only in obese women (p = 0.025 and p = 0.008, respectively). There was an interaction effect between sex and obesity, particularly among obese women (interaction p = 0.04 and 0.02, respectively). Our findings demonstrate that these SNPs have sex-specific associations with BMI in IVDD patients, and that obesity and sex, particularly among obese women, may modify the LEP transcription effect.
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Affiliation(s)
- Hsing-Hong Chen
- Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 97004, Taiwan
| | - Hsien-Ta Hsu
- Division of Neurosurgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
- School of Medicine, Buddhist Tzu Chi University, Hualien 97004, Taiwan
| | - Mei-Hsiu Liao
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
| | - Ming-Sheng Teng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
- Correspondence: ; Tel.: +886-2-6628-9779 (ext. 5790); Fax: +886-2-6628-9009
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13
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Lu W, Hu C. Molecular biomarkers for gestational diabetes mellitus and postpartum diabetes. Chin Med J (Engl) 2022; 135:1940-1951. [PMID: 36148588 PMCID: PMC9746787 DOI: 10.1097/cm9.0000000000002160] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Indexed: 11/25/2022] Open
Abstract
ABSTRACT Gestational diabetes mellitus (GDM) is a growing public health problem worldwide that threatens both maternal and fetal health. Identifying individuals at high risk for GDM and diabetes after GDM is particularly useful for early intervention and prevention of disease progression. In the last decades, a number of studies have used metabolomics, genomics, and proteomic approaches to investigate associations between biomolecules and GDM progression. These studies clearly demonstrate that various biomarkers reflect pathological changes in GDM. The established markers have potential use as screening and diagnostic tools in GDM and in postpartum diabetes research. In the present review, we summarize recent studies of metabolites, single-nucleotide polymorphisms, microRNAs, and proteins associated with GDM and its transition to postpartum diabetes, with a focus on their predictive value in screening and diagnosis.
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Affiliation(s)
- Wenqian Lu
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510630, China
- Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to the Southern Medical University, Shanghai 201400, China
| | - Cheng Hu
- Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
- The Third School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510630, China
- Department of Endocrinology and Metabolism, Fengxian Central Hospital Affiliated to the Southern Medical University, Shanghai 201400, China
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A Meta-analysis of ADIPOQ rs2241766 polymorphism association with type 2 diabetes. J Diabetes Metab Disord 2022; 21:1895-1901. [PMID: 36404807 PMCID: PMC9672214 DOI: 10.1007/s40200-022-01086-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 07/04/2022] [Indexed: 01/25/2023]
Abstract
Objective There is extensive research on the association between polymorphisms in the adiponectin gene (ADIPOQ) and type 2 diabetes (T2D). The present meta-analytic study explored the association between ADIPOQ rs2241766 polymorphisms and T2D. Metolds Articles were collected by searching Google Scholar, Scopus, and PubMed electronic databases until 2021. They were searched using a systematic search of original and sensitive English keywords and their equivalent keywords based on the keywords "type 2 diabetes", "ADIPOQ", and "rs2241766". The article selection criteria were based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram. Results The results revealed that there was no bias in this study. Some studies, such as Joshaghani et al. (odds ratio [OR] = 2.18), Hussain et al. (OR = 2.12), Momin (OR = 4.45), and Amal et al. (OR = 1.84), showed an increasing effect of ADIPOQ rs266729 polymorphism on T2D with 95% CI (P ˂ 0.01), while some have shown no significant association between them. Conclusion The results of this meta-analytic study showed the relationship between ADIPOQ and rs2241766. Also, it was found that Rs2241766 polymorphism and allele increase the risk, and rs2241766 increases the risk of developing T2D (OR = 1.29).
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Howlader M, Sultana MI, Akter F, Hossain MM. Adiponectin gene polymorphisms associated with diabetes mellitus: A descriptive review. Heliyon 2021; 7:e07851. [PMID: 34471717 PMCID: PMC8387910 DOI: 10.1016/j.heliyon.2021.e07851] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 07/17/2021] [Accepted: 08/18/2021] [Indexed: 01/24/2023] Open
Abstract
Diabetes is currently a growing concern of the age. Prevention and treatment of diabetes is a global health priority. Adiponectin is an adipocyte derived protein hormone that enhances insulin sensitivity and ameliorates diabetes by enhancing fatty acid oxidation and glucose uptake in skeletal muscle and reducing glucose production in the liver. Low serum adiponectin concentrations are associated with diabetes, central obesity, insulin resistance and metabolic syndrome. Adiponectin gene is located on chromosome 3q27, where a locus of susceptibility to diabetes was mapped. Several cross-sectional studies showed that single nucleotide polymorphisms (SNPs) in adiponectin gene (ADIPOQ) were associated with diabetes. SNPs in ADIPOQ help in assessing the association of common variants with levels of adiponectin and the risk of diabetes. Two common SNPs, rs2241766 and rs1501299, have been linked significantly to type 1 diabetes mellitus which endow the world with a block of haplotypes. Experimental evidences also suggest that rs1501299, rs2241766, rs266729, rs17366743, rs17300539, rs182052, rs822396, rs17846866, rs3774261 and rs822393 are significantly associated with type 2 diabetes mellitus which is the predominant form of the disease. In addition, rs2241766 and rs266729 are extensively associated with gestational diabetes, a condition that develops in women during pregnancy. Therefore not a particular single mutation but a number of SNPs in adiponectin gene could be a risk factor for developing diabetes among the individuals worldwide. This study firmly suggests that adiponectin plays a crucial role in the pathogenesis of type 1, type 2 and gestational diabetes mellitus.
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Affiliation(s)
- Mithu Howlader
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
| | - Mst Irin Sultana
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
| | - Farzana Akter
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
| | - Md. Murad Hossain
- Department of Biotechnology and Genetic Engineering, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh
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Dias S, Adam S, Rheeder P, Pheiffer C. No Association Between ADIPOQ or MTHFR Polymorphisms and Gestational Diabetes Mellitus in South African Women. Diabetes Metab Syndr Obes 2021; 14:791-800. [PMID: 33658815 PMCID: PMC7917309 DOI: 10.2147/dmso.s294328] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 01/16/2021] [Indexed: 12/26/2022] Open
Abstract
PURPOSE Gestational diabetes mellitus (GDM) is a growing public health concern. GDM affects approximately 14% of pregnancies globally, and without effective treatment, is associated with short- and long-term complications in mother and child. Lower serum adiponectin (ADIPOQ) concentrations and aberrant DNA methylation have been reported during GDM. The aim of this study was to investigate the association between the ADIPOQ -11377C>G and -11391G>A, and methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphisms and GDM in a population of black South African women. MATERIALS AND METHODS DNA was isolated from the peripheral blood of 447 pregnant women with (n=116) or without (n=331) GDM, where after ADIPOQ (rs266729 and rs17300539) and MTHFR (rs1801133) polymorphisms were genotyped using TaqMan Quantitative Real-Time PCR analysis. RESULTS Women with GDM had a higher body mass index (p=0.012), were more insulin resistant (p<0.001) and had lower adiponectin levels (p=0.013) compared to pregnant women with normoglycemia. Genotypic, dominant and recessive genetic models showed no association between ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms and GDM. Intriguingly, the risk G allele of ADIPOQ rs266729 was associated with higher fasting glucose and insulin concentrations, while the T allele in MTHFR rs1801133 was associated with higher fasting insulin concentrations only. CONCLUSION ADIPOQ rs266729 and rs17300539 and MTHFR rs1801133 polymorphisms are not associated with GDM in a population of black South African women. These findings suggest that these single nucleotide polymorphisms (SNPs) do not individually increase GDM risk in the African population. However, the role of these SNPs in possible gene-gene or gene-environment interactions remain to be established.
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Affiliation(s)
- Stephanie Dias
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Cape Town, 7505, South Africa
- Department of Obstetrics and Gynecology, University of Pretoria, Pretoria, 0001, South Africa
| | - Sumaiya Adam
- Department of Obstetrics and Gynecology, University of Pretoria, Pretoria, 0001, South Africa
| | - Paul Rheeder
- Department of Internal Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, 0001, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Cape Town, 7505, South Africa
- Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Cape Town, 7505, South Africa
- Correspondence: Carmen Pheiffer Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg, 7505, South AfricaTel +27 21 938 0292 Email
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Li X, He J. The Association Between Serum/Plasma Leptin Levels and Obstructive Sleep Apnea Syndrome: A Meta-Analysis and Meta-Regression. Front Endocrinol (Lausanne) 2021; 12:696418. [PMID: 34671315 PMCID: PMC8522441 DOI: 10.3389/fendo.2021.696418] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 09/07/2021] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Obstructive sleep apnea syndrome (OSAS) is associated with various adipokines. Leptin, a common adipokine, has attracted considerable attention of many researchers in recent years. So far, there has been little agreement on whether blood leptin levels differ in patients with OSAS. Thus, this meta-analysis examined the relationship between serum/plasma leptin levels and the occurrence of OSAS. METHOD WanFang, Embase, CNKI, Medline, SinoMed, Web of Science, and PubMed were searched for articles before March 30, 2021, with no language limitations. STATA version 11.0 and R software version 3.6.1 were used to analyze the obtained data. The weighted mean difference and correlation coefficients were used as the main effect sizes with a random-effects model and a fixed-effects model, respectively. Trial sequential analysis was conducted using dedicated software. RESULT Screening of 34 publications identified 45 studies that met the inclusion criteria of this meta-analysis and meta-regression. Our results suggested that plasma/serum leptin levels were remarkably higher in individuals with OSAS than in healthy individuals. Subgroup analyses were performed based on OSAS severity, ethnicity, age, body mass index, assay type, and sample source. The serum and plasma leptin levels were increased in nearly all OSAS subgroups compared to those in the corresponding control groups. Meta-regression analysis indicated that age, BMI, severity, assay approaches, study design, PSG type and ethnicity did not have independent effect on leptin levels. Furthermore, a positive relationship between the serum/plasma leptin level and apnea-hypopnea index (AHI) was found in the meta-analysis. The results of the trial sequential analysis suggested that the enrolled studies surpassed the required information size, confirming that our study findings were reliable. CONCLUSION Our study results demonstrate that OSAS patients have higher leptin levels in serum/plasma compared to controls, and the serum/plasma leptin level is positively correlated with AHI, especially in adults.
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Affiliation(s)
- Xiaoyan Li
- Department of endocrinology, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Jie He
- Department of Pulmonary and Critical Care Medicine, Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
- *Correspondence: Jie He,
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Aly O, Zaki HH, Herzalla MR, Fathy A, Raafat N, Hafez MM. Gene polymorphisms of Patatin-like phospholipase domain containing 3 (PNPLA3), adiponectin, leptin in diabetic obese patients. PLoS One 2020; 15:e0234465. [PMID: 32544194 PMCID: PMC7297308 DOI: 10.1371/journal.pone.0234465] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Accepted: 05/13/2020] [Indexed: 12/20/2022] Open
Abstract
Obesity leads a crucial importance in metabolic disorders, as well as type 2 diabetes mellitus. Our present study was designed to assess the potential role of irisin, adiponectin, leptin and gene polymorphism of PNPLA3, leptin and adiponectin as predictive markers of diabetes associated with obesity. One hundred eighty subjects were distributed to three groups including; healthy non-diabetic non obese volunteers as a control group, diabetic non obese group, and diabetic obese group (n = 60 for each group). Fasting blood samples of all groups were collected to determine fasting blood glucose, insulin levels, insulin resistance, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triacylglycerol, irisin, adiponectin, leptin; as well as, polymorphism of PNPLA3, adiponectin and leptin. The results showed that glucose, insulin resistance, total cholesterol, irisin, leptin, LDL-C, triacylglycerol concentrations were significantly increased, however, insulin, HDL-C, adiponectin were significantly decreased in diabetic obese patients in relation to diabetic non-obese patients as well as in healthy volunteers. The polymorphism of PNPLA3 rs738409 was linearly related to irisin and leptin but was not related with circulating concentrations of adiponectin. We concluded that increased irisin and leptin levels can predict the insulin resistance in obese patients. Moreover, patients who have mutant genotype of PNPLA3 I148 gene (rs738409) C>G, ADIPOQ gene (rs266729) G>C and LEP gene (rs2167270) G>A showed a significant higher susceptibility rate for DM in obese people than those with wild type. This could be considered as an adjustable retort to counter the impact of obesity on glucose homeostasis.
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Affiliation(s)
- Omnia Aly
- Department of Medical Biochemistry, National Research Centre, Cairo, Egypt
| | - Hanan Hassan Zaki
- Department of Medical Biochemistry, National Research Centre, Cairo, Egypt
| | - Mohamed R. Herzalla
- Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ahmed Fathy
- Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Nermin Raafat
- Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Mohamed M. Hafez
- Biochemistry Department, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Egypt
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Bai Y, Tang L, Li L, Li L. The roles of ADIPOQ rs266729 and MTNR1B rs10830963 polymorphisms in patients with gestational diabetes mellitus: A meta-analysis. Gene 2020; 730:144302. [DOI: 10.1016/j.gene.2019.144302] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 12/18/2019] [Accepted: 12/18/2019] [Indexed: 12/27/2022]
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Huang Q, Wang Y, Gu B, Xu Y. Whether the risk of gestational diabetes mellitus is affected by TNF-α, IL-6, IL-10 or ADIPOQ polymorphisms: a meta-analysis. Diabetol Metab Syndr 2020; 12:81. [PMID: 32963590 PMCID: PMC7499992 DOI: 10.1186/s13098-020-00582-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Accepted: 08/17/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Whether polymorphisms in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) or adiponectin (ADIPOQ) influence the risk of gestational diabetes mellitus (GDM) or not remain inconclusive. Therefore, the authors conducted a meta-analysis to robustly assess relationships between polymorphisms in TNF-α, IL-6, IL-10 or ADIPOQ and the risk of GDM by merging the results of eligible publications. METHODS A through literature searching in Medline, Embase, Wanfang, VIP and CNKI was conducted by the authors to identify eligible publications, and twenty-two publications were finally found to be eligible for merged quantitative analyses. RESULTS The merged quantitative analyses revealed that ADIPOQ + 45T/G (rs2241766) polymorphism was significantly associated with the risk of GDM in overall population (dominant comparison: OR = 0.70, p < 0.001; recessive comparison: OR = 1.95, p < 0.001; over-dominant comparison: OR = 1.18, p = 0.03; allele comparison: OR = 0.71, p < 0.001) and Asians (dominant comparison: OR = 0.70, p < 0.001; recessive comparison: OR = 1.94, p < 0.001; allele comparison: OR = 0.72, p < 0.001). Nevertheless, we did not observe any positive results for TNF-α - 238G/A (rs361525), TNF-α - 308G/A (rs1800629), IL6 - 174G/C (rs1800795), IL-10 - 819C/T (rs1800871), IL-10 - 592C/A (rs1800872), IL-10 - 1082A/G (rs1800896) and ADIPOQ + 276G/T (rs1501299) polymorphisms. CONCLUSIONS The present meta-analysis shows that among investigated TNF-α, IL-6, IL-10 or ADIPOQ polymorphisms, only ADIPOQ + 45T/G (rs2241766) polymorphism may affect the risk of GDM.
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Affiliation(s)
- Qiqi Huang
- Department of Nutrition, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 China
| | - Yi Wang
- Department of Nutrition, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 China
| | - Binbin Gu
- Department of Nutrition, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 China
| | - Yanwen Xu
- Department of Endocrinology, Huzhou Hospital of Traditional Chinese Medicine, Zhejiang University of Traditional Chinese Medicine, No.315 of South Chaoyang Street, Huzhou, 313000 China
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21
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Majcher S, Ustianowski P, Tarnowski M, Dziedziejko V, Safranow K, Pawlik A. IL-1β and IL-10 gene polymorphisms in women with gestational diabetes. J Matern Fetal Neonatal Med 2019; 34:3169-3174. [PMID: 31630588 DOI: 10.1080/14767058.2019.1678141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
AIMS Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnant women. In the GDM pathogenesis, the low-grade inflammation plays a significant role. Various inflammatory mediators are considered to be risk factors leading to GDM development including cytokines. Studies suggest that some cytokines such as: IL-1β and IL-10 play an important role in GDM pathogenesis. The aim of the study was to examine the associations between IL-1β rs16944, and IL-10 rs1800872 gene polymorphisms and GDM. METHODS This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test administered at 24-28 weeks' gestation. Among the pregnant women with GDM, 152 (75%) were treated with diet control alone throughout the pregnancy, whereas the remaining 52 (25%) were treated with diet control and insulin until delivery. RESULTS There were no statistically significant differences in the distribution of IL-1β rs16944 and IL-10 rs1800872 between GDM and healthy women. However among women treated with insulin, we observed the increased frequency of IL-1β rs16944 AA genotype carriers. Additionally, we observed increased daily insulin requirement in women with IL-1β rs16944 AA genotype. Moreover, women with IL-10 rs1800872 AA genotype had higher body mass and BMI before pregnancy as well as higher body mass and BMI increase during pregnancy. CONCLUSIONS The results of our study suggest the association between IL-1β rs16944 AA genotype and increased frequency of the need of insulin treatment as well as increased daily insulin requirement.
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Affiliation(s)
- Sandra Majcher
- Department of Physiology, Pomeranian Medical University, Szczecin, Poland
| | - Przemysław Ustianowski
- Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland
| | - Maciej Tarnowski
- Department of Physiology, Pomeranian Medical University, Szczecin, Poland
| | - Violetta Dziedziejko
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
| | - Krzysztof Safranow
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, Szczecin, Poland
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22
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Maternal Thyroid-Stimulating Hormone Level and Thyroid Peroxidase Antibody Status in the First and Second Trimester of Pregnancy and Their Relationship with the Risk of Gestational Diabetes Mellitus. MATERNAL-FETAL MEDICINE 2019. [DOI: 10.1097/fm9.0000000000000016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Wang YH, Xu XX, Sun H, Han Y, Lei ZF, Wang YC, Yan HT, Yang XJ. Cord blood leptin DNA methylation levels are associated with macrosomia during normal pregnancy. Pediatr Res 2019; 86:305-310. [PMID: 31117117 DOI: 10.1038/s41390-019-0435-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Revised: 04/25/2019] [Accepted: 05/01/2019] [Indexed: 01/29/2023]
Abstract
BACKGROUND We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia. METHOD We carried out a case-control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500-3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns (P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72-4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99-27.75), long gestational age (AOR = 3.18, 95% CI: 1.74-5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34-3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31-11.69) significantly increased the risk of macrosomia. CONCLUSIONS Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.
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Affiliation(s)
- Yu-Huan Wang
- Department of Obstetrics, Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, Zhejiang, P.R. China
| | - Xiao-Xi Xu
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, University Town, 325035, Wenzhou, Zhejiang, P.R. China
| | - Hao Sun
- Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University, 310000, Hangzhou, P.R. China
| | - Ying Han
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, University Town, 325035, Wenzhou, Zhejiang, P.R. China
| | - Zong-Feng Lei
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, University Town, 325035, Wenzhou, Zhejiang, P.R. China
| | - Yao-Cheng Wang
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, University Town, 325035, Wenzhou, Zhejiang, P.R. China
| | - Hong-Tao Yan
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, University Town, 325035, Wenzhou, Zhejiang, P.R. China
| | - Xin-Jun Yang
- Department of Preventive Medicine, School of Public Health and Management, Wenzhou Medical University, University Town, 325035, Wenzhou, Zhejiang, P.R. China.
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Cao X, Huo P, Li W, Li P, He L, Meng H. Interactions among moderate/severe periodontitis, ADIPOQ-rs1501299, and LEPR-rs1137100 polymorphisms on the risk of type 2 diabetes in a Chinese population. Arch Oral Biol 2019; 103:26-32. [PMID: 31128439 DOI: 10.1016/j.archoralbio.2019.05.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 05/05/2019] [Accepted: 05/16/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Type 2 diabetes mellitus (T2DM) is a complex disease influenced by genes and the environment. Periodontitis a demonstrated risk factor of T2DM. Previous studies related to gene-environment interactions on the risk of T2DM mainly focused on gene-obesity interactions. However, the impact of gene-periodontitis interaction on the risk of T2DM has not yet been investigated. This study aimed to investigate gene-environment interactions among moderate/severe periodontitis, polymorphisms of adiponectin (ADIPOQ)-rs1501299, and leptin receptor (LEPR)-rs1137100 on T2DM risk in Chinese subjects. DESIGN A case-control study was conducted in 239 Chinese participants from Beijing Hypertension Association Institute (BHAL). After full-mouth periodontal examinations, the participants underwent bilateral buccal swabs for DNA testing. ADIPOQ-rs1501299 and LEPR-rs1137100 were used for genotyping. Generalised multifactor dimensionality reduction (GMDR) and logistic regression were used to examine the interactions among single nucleotide polymorphisms (SNPs) and moderate/severe periodontitis on the risk of T2DM. RESULTS The risk of T2DM was higher in moderate/severe periodontitis [adjusted odds ratio (AOR) = 3.67, 95% confidence interval (95%CI): 1.26-10.71] in ADIPOQ-rs1501299 GG genotype (AOR = 3.42, 95%CI: 1.81-6.46) and LEPR-rs1137100 GG genotype (AOR = 3.16, 95%CI: 1.56-6.39). The GMDR model indicated that there was a significant three-factor model (p = 0.001) involving rs1501299, rs1137100, and moderate/severe periodontitis, demonstrating a potential gene-environment interaction among periodontitis, polymorphisms of rs1501299, and rs1137100 influencing the risk of T2DM. Moderate/severe periodontitis patients with rs1501299-GG and rs1137100-GG have the highest T2DM risk after adjusting for age, gender, BMI, WHR, smoking status, alcohol consumption, economic status, and hypertension (AOR = 20.39, 95%CI: 2.64-157.26). CONCLUSIONS Interactions among moderate/severe periodontitis, rs1501299-GG, and rs1137100-GG were associated with an increased risk of T2DM. This study may provide a new insight into the effect of gene-environment interactions on T2DM.
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Affiliation(s)
- Xiaojing Cao
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Pengcheng Huo
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Wenjing Li
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Peng Li
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Lu He
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.
| | - Huanxin Meng
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.
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Liu S, Liu Y, Liao S. Heterogeneous impact of type 2 diabetes mellitus-related genetic variants on gestational glycemic traits: review and future research needs. Mol Genet Genomics 2019; 294:811-847. [PMID: 30945019 DOI: 10.1007/s00438-019-01552-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2018] [Accepted: 03/25/2019] [Indexed: 02/07/2023]
Abstract
Gestational glucose homeostasis influences mother's metabolic health, pregnancy outcomes, fetal development and offspring growth. To understand the genetic roles in pregnant glucose metabolism and genetic predisposition for gestational diabetes (GDM), we reviewed the recent literature up to Jan, 2018 and evaluated the influence of T2DM-related genetic variants on gestational glycemic traits and glucose tolerance. A total of 140 variants of 89 genes were integrated. Their associations with glycemic traits in and outside pregnancy were compared. The genetic circumstances underlying glucose metabolism exhibit a similarity between pregnant and non-pregnant populations. While, not all of the T2DM-associated genetic variants are related to pregnant glucose tolerance, such as genes involved in fasting insulin/C-peptide regulation. Some genetic variants may have distinct effects on gestational glucose homeostasis. And certain genes may be particularly involved in this process via specific mechanisms, such as HKDC1, MTNR1B, BACE2, genes encoding cell cycle regulators, adipocyte regulators, inflammatory factors and hepatic factors related to gestational glucose sensing and insulin signaling. However, it is currently difficult to evaluate these associations with quantitative synthesis due to inadequate data, different analytical methods, varied measurements for glycemic traits, controversies in diagnosis of GDM, and unknown ethnicity- and/or sex-related influences on pregnant maternal metabolism. In conclusion, different genetic associations with glycemic traits may exist between pregnant and non-pregnant conditions. Comprehensive research on specific genetic regulation in gestation is necessary.
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Affiliation(s)
- Shasha Liu
- Diabetes Center and Transplantation Translational Medicine, Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Yihuanlu Xierduan 32#, Chengdu, 610072, China
| | - Yunqiang Liu
- Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, China
| | - Shunyao Liao
- Diabetes Center and Transplantation Translational Medicine, Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Yihuanlu Xierduan 32#, Chengdu, 610072, China.
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Circulating leptin concentration, LEP gene variants and haplotypes, and polycystic ovary syndrome in Bahraini and Tunisian Arab women. Gene 2019; 694:19-25. [DOI: 10.1016/j.gene.2019.01.032] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 12/27/2018] [Accepted: 01/22/2019] [Indexed: 02/07/2023]
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Barbe A, Bongrani A, Mellouk N, Estienne A, Kurowska P, Grandhaye J, Elfassy Y, Levy R, Rak A, Froment P, Dupont J. Mechanisms of Adiponectin Action in Fertility: An Overview from Gametogenesis to Gestation in Humans and Animal Models in Normal and Pathological Conditions. Int J Mol Sci 2019; 20:ijms20071526. [PMID: 30934676 PMCID: PMC6479753 DOI: 10.3390/ijms20071526] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Revised: 03/20/2019] [Accepted: 03/22/2019] [Indexed: 02/06/2023] Open
Abstract
Adiponectin is the most abundant plasma adipokine. It mainly derives from white adipose tissue and plays a key role in the control of energy metabolism thanks to its insulin-sensitising, anti-inflammatory, and antiatherogenic properties. In vitro and in vivo evidence shows that adiponectin could also be one of the hormones controlling the interaction between energy balance and fertility in several species, including humans. Indeed, its two receptors—AdipoR1 and AdipoR2—are expressed in hypothalamic–pituitary–gonadal axis and their activation regulates Kiss, GnRH and gonadotropin expression and/or secretion. In male gonads, adiponectin modulates several functions of both somatic and germ cells, such as steroidogenesis, proliferation, apoptosis, and oxidative stress. In females, it controls steroidogenesis of ovarian granulosa and theca cells, oocyte maturation, and embryo development. Adiponectin receptors were also found in placental and endometrial cells, suggesting that this adipokine might play a crucial role in embryo implantation, trophoblast invasion and foetal growth. The aim of this review is to characterise adiponectin expression and its mechanism of action in male and female reproductive tract. Further, since features of metabolic syndrome are associated with some reproductive diseases, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia, endometriosis, foetal growth restriction and ovarian and endometrial cancers, evidence regarding the emerging role of adiponectin in these disorders is also discussed.
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Affiliation(s)
- Alix Barbe
- INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours, F-37041 Tours, France.
| | - Alice Bongrani
- INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours, F-37041 Tours, France.
| | - Namya Mellouk
- INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours, F-37041 Tours, France.
| | - Anthony Estienne
- INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours, F-37041 Tours, France.
| | - Patrycja Kurowska
- Department of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Jagiellonian University, 31-007 Krakow, Poland.
| | - Jérémy Grandhaye
- INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours, F-37041 Tours, France.
| | - Yaelle Elfassy
- Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service de Biologie de la Reproduction, F-75020 Paris, France.
- Université Pierre et Marie Curie Paris 6, F-75005 Paris, France.
- INSERM UMRS_938, Centre de Recherche Saint-Antoine, F-75571 Paris, France.
| | - Rachel Levy
- Assistance Publique des Hôpitaux de Paris, Hôpital Tenon, Service de Biologie de la Reproduction, F-75020 Paris, France.
- Université Pierre et Marie Curie Paris 6, F-75005 Paris, France.
- INSERM UMRS_938, Centre de Recherche Saint-Antoine, F-75571 Paris, France.
| | - Agnieszka Rak
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
| | - Pascal Froment
- INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours, F-37041 Tours, France.
| | - Joëlle Dupont
- INRA UMR85 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- CNRS UMR7247 Physiologie de la Reproduction et des Comportements, F-37380 Nouzilly, France.
- Université François Rabelais de Tours, F-37041 Tours, France.
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Huang LT, Wu SL, Liao X, Ma SJ, Tan HZ. Adiponectin gene polymorphisms and risk of gestational diabetes mellitus: A meta-analysis. World J Clin Cases 2019; 7:572-584. [PMID: 30863757 PMCID: PMC6406200 DOI: 10.12998/wjcc.v7.i5.572] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 12/24/2018] [Accepted: 01/03/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Adiponectin (ADIPOQ) is an important factor involved in the regulation of both carbohydrate and lipid metabolism. Polymorphisms in the ADIPOQ gene are known to influence an individual’s predisposition to metabolic syndrome and type 2 diabetes. Moreover, women with gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes. Several studies have been conducted previously to assess the association between ADIPOQ polymorphisms and GDM; however, the results of the association are inconclusive.
AIM To quantitatively evaluate the association between ADIPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM.
METHODS A systematic search of EMBASE, PubMed, CNKI, Web of Science, and WANFANG DATA was conducted up to October 20, 2018. We calculated merged odds ratios (ORs) with 95% confidence intervals (CIs) using a fixed-effects or random-effects model depending on the between-study heterogeneity to evaluate the association between AIDPOQ +45T/G, +276G/T, and -11377C/G polymorphisms and the risk of GDM. Subgroup analysis was performed by ethnicity. Publication and sensitivity bias analyses were performed to test the robustness of the association. All statistical analyses were conducted using Stata12.0.
RESULTS Nine studies of +45T/G included 1024 GDM cases and 1059 controls, five studies of +276G/T included 590 GDM cases and 595 controls, and five studies of -11377C/G included 722 GDM cases and 791 controls. Pooled ORs indicated that +45T/G increased GDM risk in Asians (allelic model: OR = 1.47, 95%CI: 1.27-1.70, P = 0.000; dominant model: OR = 1.54, 95%CI: 1.27-1.85, P = 0.000; recessive model: OR=2.00, 95%CI: 1.43-2.85, P = 0.000), not in South Americans (allelic model: OR = 1.21, 95%CI: 0.68-2.41, P = 0.510; dominant model: OR = 1.13, 95%CI: 0.59-2.15, P = 0.710; recessive model: OR = 2.18, 95%CI: 0.43-11.07, P = 0.350). There were no significant associations between +276G/T (allelic model: OR = 0.88, 95%CI: 0.74-1.05, P = 0.158; dominant model: OR = 0.91, 95%CI: 0.65-1.26, P = 0.561; recessive model: OR = 0.82, 95%CI: 0.64-1.05, P = 0.118) or -11377C/G (allelic model: OR = 0.96, 95%CI: 0.72-1.26, P = 0.750; dominant model: OR = 1.00, 95%CI: 0.73-1.37, P = 0.980; recessive model: OR = 0.90, 95%CI: 0.61-1.32, P = 0.570) and the risk of GDM.
CONCLUSION Our meta-analysis shows the critical role of the ADIPOQ +45T/G polymorphism in GDM, especially in Asians. Studies focused on delineating ethnicity-specific factors with larger sample sizes are needed.
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Affiliation(s)
- Lin-Ting Huang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410083, Hunan Province, China
| | - Shi-Lan Wu
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410083, Hunan Province, China
| | - Xin Liao
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410083, Hunan Province, China
| | - Shu-Juan Ma
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410083, Hunan Province, China
| | - Hong-Zhuan Tan
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha 410083, Hunan Province, China
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Michita RT, Kaminski VDL, Chies JAB. Genetic Variants in Preeclampsia: Lessons From Studies in Latin-American Populations. Front Physiol 2018; 9:1771. [PMID: 30618791 PMCID: PMC6302048 DOI: 10.3389/fphys.2018.01771] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 11/23/2018] [Indexed: 12/13/2022] Open
Abstract
Placental vascularization is a tightly regulated physiological process in which the maternal immune system plays a fundamental role. Vascularization of the maternal-placental interface involves a wide range of mechanisms primarily orchestrated by the fetal extravillous trophoblast and maternal immune cells. In a healthy pregnancy, an immune cross-talk between the mother and fetal cells results in the secretion of immunomodulatory mediators, apoptosis of specific cells, cellular differentiation/proliferation, angiogenesis, and vasculogenesis, altogether favoring a suitable microenvironment for the developing embryo. In the context of vasculopathy underlying common pregnancy disorders, it is believed that inefficient invasion of extravillous trophoblast cells in the endometrium leads to a poor placental blood supply, which, in turn, leads to decreased secretion of angiogenic factors, hypoxia, and inflammation commonly associated with preterm delivery, intrauterine growth restriction, and preeclampsia. In this review, we will focus on studies published by Latin American research groups, providing an extensive review of the role of genetic variants from candidate genes involved in a broad spectrum of biological processes underlying the pathophysiology of preeclampsia. In addition, we will discuss how these studies contribute to fill gaps in the current understanding of preeclampsia. Finally, we discuss some trending topics from important fields associated with pregnancy vascular disorders (e.g., epigenetics, transplantation biology, and non-coding RNAs) and underscore their possible implications in the pathophysiology of preeclampsia. As a result, these efforts are expected to give an overview of the extent of scientific research produced in Latin America and encourage multicentric collaborations by highlighted regional research groups involved in preeclampsia investigation.
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Affiliation(s)
- Rafael Tomoya Michita
- Immunogenetics Laboratory, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Valéria de Lima Kaminski
- Immunogenetics Laboratory, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - José Artur Bogo Chies
- Immunogenetics Laboratory, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
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Molecular Biomarkers for Gestational Diabetes Mellitus. Int J Mol Sci 2018; 19:ijms19102926. [PMID: 30261627 PMCID: PMC6213110 DOI: 10.3390/ijms19102926] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 09/21/2018] [Accepted: 09/22/2018] [Indexed: 12/20/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included “gestational diabetes mellitus”, “blood”, “single-nucleotide polymorphism (SNP)”, “DNA methylation”, and “microRNAs”, including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.
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Association between chemerin rs17173608 and rs4721 gene polymorphisms and gestational diabetes mellitus in Iranian pregnant women. Gene 2018; 649:87-92. [DOI: 10.1016/j.gene.2018.01.061] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Revised: 12/18/2017] [Accepted: 01/17/2018] [Indexed: 12/18/2022]
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Association of adiponectin gene variants with idiopathic recurrent miscarriage according to obesity status: a case-control study. J Transl Med 2018; 16:76. [PMID: 29559003 PMCID: PMC5861597 DOI: 10.1186/s12967-018-1453-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 03/15/2018] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND This study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity. METHODS Retrospective case-control study performed in outpatient obstetrics/gynecology clinics. Study subjects comprised 308 women with RPL, defined as ≥ 3 consecutive miscarriages of unknown etiology, and 310 control women. ADIPOQ genotyping was done by allele exclusion method on real-time PCR. RESULTS Of the 14 ADIPOQ variants tested, the minor allele frequency (MAF) of rs4632532, rs17300539, rs266729, rs182052, rs16861209, and rs7649121 were significantly higher, while rs2241767, and rs1063539 MAF were lower in RPL cases, hence assigning RPL-susceptibility and protection to these variants, respectively. Higher frequencies of heterozygous rs17300539 and rs16861209, and homozygous rs4632532, rs266729, and rs182052 genotypes, and reduced frequencies of heterozygous rs1063539 and rs2241767, homozygous rs2241766 genotypes were seen in RPL cases. ADIPOQ rs4632532, and rs2241766 were associated with RPL in obese, while rs1063539 and rs16861209 were associated with RPL in non-obese women; rs182052 and rs7649121 associated with RPL independently of BMI changes. Based on LD pattern, two haplotype blocks were identified. Within Block 1 containing rs4632532, rs16861194, rs17300539, rs266729, rs182052, rs16861209, rs822396, and rs7649121, increased frequency of CAGGACAT and TAACGAAA, and reduced frequency of TAGCGCAA haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection, respectively. CONCLUSION This is the first study to document contribution of ADIPOQ variants and haplotypes with RPL, and also to underscore the contribution of obesity to genetic association studies.
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Zhao L, Sun T, Wang L. Chitosan oligosaccharide improves the therapeutic efficacy of sitagliptin for the therapy of Chinese elderly patients with type 2 diabetes mellitus. Ther Clin Risk Manag 2017; 13:739-750. [PMID: 28721055 PMCID: PMC5499789 DOI: 10.2147/tcrm.s134039] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
Sitagliptin improves glycemic control in type 2 diabetes mellitus (T2DM) patients but its side effects are undesirable. Chitosan oligosaccharide (COS) is expected to improve the therapeutic result as a natural product. A total of 200 elderly T2DM patients were evenly assigned into four groups: sitagliptin group (SG), receiving sitagliptin 100 mg/day; COS group (CG), receiving COS 100 mg/day; combination therapy of sitagliptin and COS group (SCG), receiving both sitagliptin and COS 100 mg/day; and placebo group (PG), receiving placebo 100 mg/day. After 42-week therapy, biochemical indices and clinical parameters for the alterations from start points were analyzed. The related molecular mechanism was tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot at cell level. Lower risk of hypoglycemia was found in the SCG group when compared with SG and other groups (P<0.05). More patients from the SCG group than other groups attained hemoglobin A1c (HbA1c) reduction >2.5% (P<0.05). Weight reduction of 1.2±0.9, 2.6±0.8, 4.7±1.3, and 0.9±0.6 kg was observed in the patients from SG, CG, SCG, and PG groups, respectively (P<0.05). The combined treatment of COS and sitagliptin presented better therapeutic results by improving insulin sensitivity, lipid profile, adiponectin levels, and glucagon-like peptide 1 and reducing side effects, insulin resistance, HbA1c, body mass index, resistin, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) (P<0.05). qRT-PCR and Western blot analysis also showed that COS treatment reduced the levels of resistin, TNF-α, and CRP, and increased the level of adiponectin. The combination of COS and sitagliptin provided better glycemic control with fewer side effects and with more weight reduction in the elderly participants with T2DM.
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Affiliation(s)
| | - Tingli Sun
- Department of Nephrology, General Hospital of Daqing Oil Field, Daqing, China
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