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1
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Harun-Or-Roshid M, Nurul Haque Mollah M, Jesmin. Association of IL6 Gene Polymorphisms and Neurological Disorders: Insights from Integrated Bioinformatics and Meta-Analysis. Neuromolecular Med 2025; 27:9. [PMID: 39812719 DOI: 10.1007/s12017-025-08831-7] [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: 10/27/2024] [Accepted: 01/08/2025] [Indexed: 01/16/2025]
Abstract
Interleukin 6 (IL6) is an inflammatory biomarker linked to central and peripheral nervous system diseases. This study combined bioinformatics and statistical meta-analysis to explore potential associations between IL6 gene variants (rs1800795, rs1800796, and rs1800797) and neurological disorders (NDs) and brain cancer. The meta-analysis was conducted on substantial case-control datasets and revealed a significant correlation between IL6 SNPs (rs1800795 and rs1800796) with overall NDs (p-value < 0.05). The disease-stratified analysis of rs1800795 revealed significant correlations with Schizophrenia, Alzheimer's, and Parkinson's diseases (p-value < 0.05), while rs1800796 showed a substantial connection with Celiac disease (p-value < 0.05). The ethnicity-stratified analysis revealed noteworthy associations between rs1800795 in both Asians and Caucasians (p-value < 0.05), while rs1800796 showed significant associations across all ethnic groups analyzed (p-value < 0.05). Furthermore, integrated Bioinformatics analyses using GTEx and TCGA datasets highlighted IL6's involvement in NDs and its potential role in brain cancer. Specifically, IL6 SNPs (rs1800795 and rs1800797) showed a significant association with Glioma (p-value < 0.001). Copy number alterations and increased IL6 expressions were linked to cancer severity (p-value < 0.001) and hypoxia (p-value < 0.0001). Kaplan-Meier survival analysis demonstrated that elevated IL6 expression was strongly associated with decreased overall survival in brain cancer patients (p-value < 0.0001). In conclusion, this study identified notable correlations between IL6 SNPs and NDs, underscoring their potential as valuable prognostic biomarkers for various neurological conditions.
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Affiliation(s)
| | | | - Jesmin
- Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh.
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Gaba K, Malhotra P, Kumar A, Suneja P, Dang AS. Understanding the Genetic Basis of Celiac Disease: A Comprehensive Review. Cell Biochem Biophys 2024; 82:1797-1808. [PMID: 38907939 DOI: 10.1007/s12013-024-01371-0] [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] [Accepted: 06/16/2024] [Indexed: 06/24/2024]
Abstract
Celiac disease is an immune-mediated enteropathy with typical symptoms of weight loss, abdominal bloating, diarrhea, vomiting, or constipation. Many shreds of evidence show that CeD is hereditary in origin and various biochemical pathways have been connected to its etiology. Numerous genes from different physiological pathways have been investigated in the last few decades, however a comprehensive analysis is required to address the gaps and provide a more integrated understanding of how these genetic factors contribute to the pathogenesis of disease. Present study attempts to summarize the historical and up-to-date findings to understand the role of genetics in Celiac disease. The literature was searched from sources such as PubMed and Google Scholar to analyze studies conducted on celiac disease from the years 1995 to 2024. Term maps were created to examine the frequency of studies related to various terms to understand the major focus of the studies till date. The study also concise the different genetic polymorphisms studied in a table to understand the role of genetics in celiac diseases. Early studies on celiac disease primarily focused on its pathophysiology, prevalence, and general aspects, with limited attention to genetics. However, recent studies have increasingly emphasized the genetic basis of the disease and highlighting the involvement of various pathways like inflammation, T-cell differentiation and activation, epithelial barrier function, stress and apoptosis pathways. However, present study indicate that most current research predominantly focus on cytokines, specifically the TNF alpha gene. Consequently, there is a need for additional research to gain a more comprehensive understanding of the genetics of celiac disease.
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Affiliation(s)
- Kajal Gaba
- Centre For Medical Biotechnology, Maharshi Dayanand University, Rohtak, 124001, India
| | | | - Anil Kumar
- Centre For Medical Biotechnology, Maharshi Dayanand University, Rohtak, 124001, India
| | - Pooja Suneja
- Department of Microbiology, Maharshi Dayanand University, Rohtak, 124001, India
| | - Amita Suneja Dang
- Centre For Medical Biotechnology, Maharshi Dayanand University, Rohtak, 124001, India.
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3
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Lupu VV, Sasaran MO, Jechel E, Starcea IM, Ioniuc I, Mocanu A, Rosu ST, Munteanu V, Nedelcu AH, Danielescu C, Salaru DL, Knieling A, Lupu A. Celiac disease - a pluripathological model in pediatric practice. Front Immunol 2024; 15:1390755. [PMID: 38715620 PMCID: PMC11074362 DOI: 10.3389/fimmu.2024.1390755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 04/03/2024] [Indexed: 05/23/2024] Open
Abstract
Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.
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Affiliation(s)
- Vasile Valeriu Lupu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Maria Oana Sasaran
- Faculty of Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, Targu Mures, Romania
| | - Elena Jechel
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | | | - Ileana Ioniuc
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Adriana Mocanu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Solange Tamara Rosu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Valentin Munteanu
- Faculty of Medical Bioengineering, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Alin Horatiu Nedelcu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Ciprian Danielescu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Delia Lidia Salaru
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Anton Knieling
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
| | - Ancuta Lupu
- Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iasi, Romania
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Aliyu M, Zohora FT, Anka AU, Ali K, Maleknia S, Saffarioun M, Azizi G. Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach. Int Immunopharmacol 2022; 111:109130. [PMID: 35969896 DOI: 10.1016/j.intimp.2022.109130] [Citation(s) in RCA: 112] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/26/2022] [Accepted: 08/03/2022] [Indexed: 12/19/2022]
Abstract
Several studies have shown that interleukin 6 (IL-6) is a multifunctional cytokine with both pro-inflammatory and anti-inflammatory activity, depending on the immune response context. Macrophages are among several cells that secrete IL-6, which they express upon activation by antigens, subsequently inducing fever and production of acute-phase proteins from the liver. Moreover, IL-6 induces the final maturation of B cells into memory B cells and plasma cells as well as an adaptive role for short-term energy allocation. Activation of IL-6 receptors results in the intracellular activation of the JAK/STAT pathway with resultant production of inflammatory cytokines. Several mechanisms-controlled IL-6 expression, but aberrant production was shown to be crucial in the pathogenesis of many diseases, which include autoimmune and chronic inflammatory diseases. IL-6 in combination with transforming growth factor β (TGF-β) induced differentiation of naïve T cells to Th17 cells, which is the cornerstone in autoimmune diseases. Recently, IL-6 secretion was shown to form the backbone of hypercytokinemia seen in the Coronavirus disease 2019 (COVID-19)-associated hyperinflammation and multiorgan failure. There are two classes of approved IL-6 inhibitors: anti-IL-6 receptor monoclonal antibodies (e.g., tocilizumab) and anti-IL-6 monoclonal antibodies (i.e., siltuximab). These drugs have been evaluated in patients with rheumatoid arthritis, juvenile idiopathic arthritis, cytokine release syndrome, and COVID-19 who have systemic inflammation. JAK/STAT pathway blockers were also successfully used in dampening IL-6 signal transduction. A better understanding of different mechanisms that modulate IL-6 expression will provide the much-needed solution with excellent safety and efficacy profiles for the treatment of autoimmune and inflammatory diseases in which IL-6 derives their pathogenesis.
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Affiliation(s)
- Mansur Aliyu
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-IC, Tehran, Iran; Department of Medical Microbiology, Faculty of Clinical Science, College of Health Sciences, Bayero University, Kano, Nigeria
| | - Fatema Tuz Zohora
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Malaysia
| | - Abubakar Umar Anka
- Department of Medical Laboratory Science, College of Medical Sciences, Ahmadu Bello University, Zaria, Nigeria
| | - Kashif Ali
- Department of Pharmacy Abdul Wali, Khan University Mardan, Pakistan
| | - Shayan Maleknia
- Biopharmaceutical Research Center, AryoGen Pharmed Inc., Alborz University of Medical Sciences, Karaj, Iran
| | - Mohammad Saffarioun
- Biopharmaceutical Research Center, AryoGen Pharmed Inc., Alborz University of Medical Sciences, Karaj, Iran
| | - Gholamreza Azizi
- Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.
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Zhang JZ, Abudoureyimu D, Wang M, Yu SR, Kang XJ. Association between celiac disease and vitiligo: A review of the literature. World J Clin Cases 2021; 9:10430-10437. [PMID: 35004975 PMCID: PMC8686139 DOI: 10.12998/wjcc.v9.i34.10430] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 06/25/2021] [Accepted: 10/20/2021] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an autoimmune intestinal disease caused by the intake of gluten-containing cereals and their products by individuals with genetic susceptibility genes. Vitiligo is a commonly acquired depigmentation of the skin; its clinical manifestation are skin patches caused by localized or generalized melanin deficiency. Both diseases have similar global incidence rates (approximately 1%) and are associated to similar diseases, including autoimmune bullous disease, inflammatory bowel disease, autoimmune thyroiditis, autoimmune gastritis, and type 1 diabetes. The relationship between CD and vitiligo has been reported in several studies, but their conclusions are inconsistent. Further, it has also been reported that a gluten-free diet (GFD) can improve the symptoms of immune-related skin diseases such as vitiligo. In this mini-review, we summarize and review the literature on the relationship between CD and vitiligo, assess the therapeutic significance of GFD for patients with vitiligo, and explore their possible physiopathology. We are hopeful that the information summarized here will assist physicians who treat patients with CD or vitiligo, thereby improving the prognosis.
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Affiliation(s)
- Jing-Zhan Zhang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Dilinuer Abudoureyimu
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Man Wang
- Department of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Shi-Rong Yu
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
| | - Xiao-Jing Kang
- Department of Dermatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Key Laboratory of Dermatology Research, Urumqi 830001, Xinjiang Uygur Autonomous Region, China
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Karcioglu Batur L, Hekim N. Correlation between interleukin gene polymorphisms and current prevalence and mortality rates due to novel coronavirus disease 2019 (COVID-2019) in 23 countries. J Med Virol 2021; 93:5853-5863. [PMID: 34081354 PMCID: PMC8242628 DOI: 10.1002/jmv.27127] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 06/01/2021] [Indexed: 12/26/2022]
Abstract
Background The novel coronavirus disease 2019 (COVID‐19) infection may rely on a potential genetic background for the variations in the inflammatory response. We aimed to investigate the possible correlation between polymorphisms in the IL‐6 gene at rs1800796/rs1800795, in IL‐6R at rs2228145, in IL‐10 at rs1800896 and rs1800871, in IL‐17 at rs2275913 and rs763780 loci, and COVID‐19 prevalence and mortality rates among populations of 23 countries. Methods We searched the literature for polymorphisms in China, Japan, India, Spain, Mexico, Sweden, Turkey, Brazil, Russia, Poland, Italy, South Africa, Netherlands, Greece, Germany, UK, Iran, Finland, Czechia, Tunisia, Norway, Egypt, Croatia. We recorded the prevalence and mortality rates (per million) caused by the Coronavirus infection recorded on 7th September 2020 and 6th December 2020. Results There was a significant positive correlation between the frequency of AG genotype of rs1800896 and prevalence recorded on 6th December 2020 (r: 0.53, r2: 0.28, p < .05). There was a significant negative correlation between the mortality rates recorded on 7th September, and the AG genotype of rs2275913 (r: −0.51, r2: 0.26, p < .05). There was a significant positive correlation between the prevalence recorded on 6th December, and TT genotype at rs763780 (r: 0.65, r2:0.42, p < .05) while a negative correlation between prevalence and TC genotype at rs763780 (r: −0.66, r2: 0.43, p < .05). Also, a significant negative correlation was found between mortality rates recorded on 6th December 2020 and CC genotype at rs763780 (r: −0.56, r2: 0.31, p < .05). Conclusion The variations in prevalence of COVID‐19 and its mortality rates among countries may be explained by the polymorphisms at rs1800896 in IL‐10, rs2275913 in IL‐17A, and rs763780 loci in the IL‐17F gene.
The variations in prevalence of COVID‐19 and its mortality rates among 23 countries may be explained by the polymorphisms at rs1800896 in IL‐10, rs2275913 in IL‐17A, and rs763780 loci in the IL‐17F gene. AG genotype frequency of rs1800896 was positively correlated with prevalence recorded on 6th December 2020. The mortality rates recorded on 7th September was negatively correlated with AG genotype frequency of rs2275913. The prevalence recorded on 6th December was positively correlated with frequency of TT and negatively with TC genotype at rs763780. The mortality rates recorded on 6th December 2020 was negatively correlated with CC genotype frequency at rs763780.
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Affiliation(s)
- Lutfiye Karcioglu Batur
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, Turkey
| | - Nezih Hekim
- Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Biruni University, Istanbul, Turkey
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Eldem A, Ayna TK, Baran M, Soyöz M, Pirim İ. Determination of High-Resolution HLA-DQB1 Suballeles and IL-17 Polymorphisms in Turkish Pediatric Patients. J Pediatr Genet 2021; 11:192-197. [DOI: 10.1055/s-0041-1722856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 12/12/2020] [Indexed: 10/22/2022]
Abstract
AbstractCeliac disease (CD) is an autoimmune enteropathy in the small intestine caused by gluten intolerance of the patients. The most important genetic disease-related factor is human leukocyte antigen (HLA)-DQ polymorphism. Association between interleukin (IL)-17A expression of CD4+ T cells and various autoimmune diseases has been reported. The aim of this study was to investigate the relationship between single nucleotide polymorphism (rs2275913) IL-17A and HLA-DQ polymorphisms in Turkish pediatric celiac patients. Study group included 125 pediatric celiac patients with CD and 100 healthy pediatric controls. Deoxyribonucleic acid was isolated from peripheral blood samples. IL-17A polymorphism (rs2275913) was analyzed by polymerase chain reaction-restriction fragment polymorphism method. IL-17A polymorphism and low-/high-resolution HLA-DQ results of patients were evaluated. GG and GA genotype frequencies of IL-17A (rs2275913) polymorphism were significantly higher (p < 0.05) in the CD patients than the control group. HLA-DQB1*02 and HLA-DQA1*05 alleles were detected in patients, while HLA-DQB1*03 and HLA-DQA1*01 alleles in the control group. Also, when we compared the patient and control groups in terms of HLA-DQ-DR haplotypes, HLA-DQB1*02-DQA1*05-DRB1*03 was found with the relative risk of 42.5 (p < 0.05). As a result of high-resolution HLA-DQB1 typing, DQB1*02:01 and DQB1*03:02 were at high frequency (p < 0.05; in 25 patient group). IL-17A (rs2275913) polymorphism genotype frequency was found to be significant in the patient group compared with the control group. The most common HLA-DQB1 suballele was observed as DQB1*02:01.
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Affiliation(s)
- Aslı Eldem
- Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey
| | - Tülay Kılıçaslan Ayna
- Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey
| | - Maşallah Baran
- Department of Pediatric Gastroenterology, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital, İzmir, Turkey
| | - Mustafa Soyöz
- Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey
| | - İbrahim Pirim
- Department of Medical Biology and Genetics, Izmir Katip Celebi University, Izmir Tepecik Education and Research Hospital Tissue Typing Laboratory, İzmir, Turkey
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Kurnaz S, Yazici AB, Nursal AF, Cetinay Aydin P, Ongel Atar A, Aydin N, Kincir Z, Pehlivan S. CNR2 rs2229579 and COMT Val158Met variants, but not CNR2 rs2501432, IL-17 rs763780 and UCP2 rs659366, contribute to susceptibility to substance use disorder in the Turkish population. PSYCHIAT CLIN PSYCH 2019. [DOI: 10.1080/24750573.2019.1688030] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Affiliation(s)
- Selin Kurnaz
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ahmet Bulent Yazici
- Department of Psychiatry, Sakarya University Training and Research Hospital, Sakarya, Turkey
| | - Ayse Feyda Nursal
- Department of Medical Genetics, Faculty of Medicine, Hitit University, Corum, Turkey
| | - Pinar Cetinay Aydin
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Ayca Ongel Atar
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Nazan Aydin
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Zeliha Kincir
- Department of Psychiatry, Bakirkoy Mazhar Osman Training and Research Hospital for Psychiatry, Istanbul, Turkey
| | - Sacide Pehlivan
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Işık İA, Akbulut UE. The coexistence of neurofibromatosis type I and celiac disease in a child. TURKISH JOURNAL OF GASTROENTEROLOGY 2019; 29:522-523. [PMID: 30249573 DOI: 10.5152/tjg.2018.18053] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- İshak Abdurrahman Işık
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Health Sciences University Antalya
| | - Ulaş Emre Akbulut
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Health Sciences University Antalya
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Barartabar Z, Nikzamir A, Sirati-Sabet M, Aghamohammadi E, Chaleshi V, Rostami Nejad M, Asadzadeh-Aghdaei H, Reza Zali M. The relationship between 174 G/C and -572 G/C of IL-6 gene polymorphisms and susceptibility of celiac disease in the Iranian population. PRZEGLAD GASTROENTEROLOGICZNY 2018; 13:293-298. [PMID: 30581503 PMCID: PMC6300853 DOI: 10.5114/pg.2018.79808] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Accepted: 06/07/2018] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Celiac disease (CD) is a chronic inflammatory intestinal disorder. Different immunological factors, including inflammatory cytokines, may play an important role in disease susceptibility. AIM To investigate the relationship between -174G/C and -572G/C gene polymorphisms and the serum level of interleukin 6 (IL-6) and susceptibility to CD in the Iranian population. MATERIAL AND METHODS In this case-control study blood samples were collected of 105 patients with CD and 106 healthy subjects randomly in 2016 and evaluated by polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) method. A sequence was also used to confirm the results of both polymorphisms. The IL-6 concentration was measured using ELISA. RESULTS The results showed a significant relationship between polymorphism -572G in CD patients when compared with control subjects by genotype (p = 0.001) and alleles (p = 0.022), respectively. There was no significant relationship between polymorphism 174G and frequency of genotype, but an association of this polymorphism with the frequency of alleles (p = 0.034), age (p = 0.001), and body mass index (p = 0.003) was seen. The serum level of interleukin-6 was significantly associated only with rs1800796 (p < 0.001). CONCLUSIONS The results confirm previous studies in different parts of the world and indicate that IL-6 (572G/C) polymorphism may play a role in susceptibility to CD in the Iranian population.
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Affiliation(s)
- Zeinab Barartabar
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
| | - Abdolrahim Nikzamir
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
| | - Majid Sirati-Sabet
- Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
| | - Elham Aghamohammadi
- Gastroenterology and Liver Diseases Research Centre, Research Institute for
Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
| | - Vahid Chaleshi
- Gastroenterology and Liver Diseases Research Centre, Research Institute for
Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
| | - Mohammad Rostami Nejad
- Gastroenterology and Liver Diseases Research Centre, Research Institute for
Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
| | - Hamid Asadzadeh-Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research
Centre, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti
University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Centre, Research Institute for
Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran,
Iran
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Omidian Z, Ahmed R, Giwa A, Donner T, Hamad ARA. IL-17 and limits of success. Cell Immunol 2018; 339:33-40. [PMID: 30765202 DOI: 10.1016/j.cellimm.2018.09.001] [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: 07/13/2018] [Accepted: 09/15/2018] [Indexed: 12/14/2022]
Abstract
Interleukin-17 (IL-17) is a potent proinflammatory cytokine that protects a host against fungal and extracellular bacterial infections. On the other hand, excessive or dysregulated production of IL-17 underlines susceptibility to autoimmune disease. Consequently, blocking IL-17 has become an effective strategy for modulating several autoimmune diseases, including multiple sclerosis (MS), psoriasis, and rheumatoid arthritis (RA). Notably, however, IL-17 blockade remains ineffective or even pathogenic against important autoimmune diseases such as inflammatory bowel disease (IBD). Furthermore, the efficacy of IL-17 blockade against other autoimmune diseases, including type 1 diabetes (T1D) is currently unknown and waiting results of ongoing clinical trials. Coming years will determine whether the efficacy of IL-17 blockade is limited to certain autoimmune diseases or can be expanded to other autoimmune diseases. These efforts include new clinical trials aimed at testing second-generation agents with the goal of increasing the efficiency, spectrum, and ameliorating side effects of IL-17 blockade. Here we briefly review the roles of IL-17 in the pathogenesis of selected autoimmune diseases and provide updates on ongoing and recently completed trials of IL-17 based immunotherapies.
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Affiliation(s)
- Zahra Omidian
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
| | - Rizwan Ahmed
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
| | - Adebola Giwa
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
| | - Thomas Donner
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States
| | - Abdel Rahim A Hamad
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
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Shahramian I, Bazi A, Sargazi A. An Overview of Celiac Disease in Childhood Type 1 Diabetes. Int J Endocrinol Metab 2018; 16:e66801. [PMID: 30214462 PMCID: PMC6119207 DOI: 10.5812/ijem.66801] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2018] [Revised: 06/09/2018] [Accepted: 06/13/2018] [Indexed: 02/08/2023] Open
Abstract
CONTEXT Celiac disease (CD) is a common phenomenon in children with Type 1 diabetes (T1D). In the present review, we have discussed the pathogenesis, diagnostic biomarkers, risk factors, and prognosis of CD in the context of pediatric T1D. EVIDENCE ACQUISITION Literature published in Web of Science, PubMed, Scopus, Google Scholar, and Cochrane Library were scrutinized up to the end of 2017. The keywords of celiac disease, Type 1 diabetes, children, and pediatric were used in different combinations. RESULTS Immune cytotoxic reactions along with dampen immune regulatory functions contribute to CD in the context of pediatric T1D. Many children with simultaneous CD and T1D do not represent with the clinical signs of the enteropathy rendering a diagnostic challenge. The most common screening tests in these children are routine serological tests of CD, anti - endomysial, anti - transglutaminase, and anti - deamidated gliadin peptide antibodies. Typing for human leukocyte antigens of DQ - 2 and DQ - 8 may assist in the diagnosis of silent CD in children with T1D. The most significant shared non - HLA genetic loci of CD and T1D comprise CTLA - 4, TAGAP, IL - 18RAP, PTPN2, RGS1, SH2B3, CCR5. Interactions between these loci can be important in susceptibility to CD in T1D. Some new biomarkers have been suggested for diagnosis of CD including ischemia-modified albumin (IMA), soluble syndecan-1 (SSDC-1), regenerating gene Iα (REG-Iα), Neurotensin, and Zonulin, which can be useful for diagnosis and screening of CD in childhood T1D. CONCLUSIONS Overall, active seropositive CD seems to be of clinical importance in T1D with significant impacts on the quality of life and predisposition to diabetes associated complications. It is important to detect CD in the context of T1D to prevent potential risks contributing to morbidities and mortalities associated with either CD or T1D.
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Affiliation(s)
- Iraj Shahramian
- Pediatric Ward, Amir - Al - Momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran
| | - Ali Bazi
- Clinical Research Development Unit, Amir - Al - Momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran
| | - Alireza Sargazi
- Student Research Committee, Zabol University of Medical Sciences, Zabol, Iran
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