Lack of association between rs1800795 (-174 G/C) polymorphism in the promoter region of interleukin-6 gene and susceptibility to type 2 diabetes in Isfahan population

Ghavimi, Reza; Sharifi, Mohammadreza; Mohaghegh, Mohammad Ali; Mohammadian, Hossein; Khadempar, Saedeh; Rezaei, Hamzeh

Lack of association between rs1800795 (-174 G/C) polymorphism in the promoter region of interleukin-6 gene and susceptibility to type 2 diabetes in Isfahan population

Authors

¹ Department of Pharmaceutical Biotechnology, Isfahan University of Medical Sciences, Isfahan, Iran

² Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan, Iran

³ Department of Parasitology and Mycology, Isfahan University of Medical Sciences, Isfahan, Iran

⁴ Department of Biology, Kurdistan Science and Research Branch, Islamic Azad University, Sanandaj, Iran

⁵ Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran

Abstract

Background: Type 2 diabetes mellitus (T2DM) is an inflammatory autoimmune disease that mostly affects older adults. The etiology of T2DM includes both genetic and environmental factors. rs1800795 (−174 G/C) single nucleotide polymorphism (SNP) linked with autoimmune disorders predispositions, identified by Genome-Wide Association Study among genes, which immunologically related is considerably over signified. The goal of this study was to evaluate the association between rs1800795 (−174 G/C) polymorphisms in the promoter of interleukin-6 (IL-6) gene with susceptibility to T2DM in a subset of the Iranian population.
Materials and Methods: In this case–control study, 120 healthy subjects and 120 patients with T2DM were included. Genomic DNA obtained from whole blood samples and the polymerase chain reaction was used to amplify the fragment of interest contain rs1800795 SNP, restriction fragment length polymorphism method was applied for genotyping of the DNA samples with NlaIII as a restriction enzyme. SPSS for Windows software (version 18.0, SPSS, Chicago, IL, USA) was performed for statistical analysis.
Results: No significant differences were found between healthy controls and T2DM patients with respect to the frequency distribution of the cytokine gene polymorphism investigated. Odds ratio, adjusted for sex, age, and smoking status has displayed similar outcomes.
Conclusion: These results indicated that the rs1800795 SNP is not a susceptibility gene variant for the development of T2DM in the Isfahan population. Further studies using new data on complex transcriptional interactions between IL-6 polymorphic sites are necessary to determine IL-6 haplotype influence on susceptibility to T2DM.

Keywords

References

1.	Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus – Present and future perspectives. Nat Rev Endocrinol 2011;8:228-36.
2.	Zimmet PZ, Magliano DJ, Herman WH, Shaw JE. Diabetes: A 21^st century challenge. Lancet Diabetes Endocrinol 2014;2:56-64.
3.	Maruthur NM. The growing prevalence of type 2 diabetes: Increased incidence or improved survival? Curr Diab Rep 2013;13:786-94.
4.	Bao W, Hu FB, Rong S, Rong Y, Bowers K, Schisterman EF, et al. Predicting risk of type 2 diabetes mellitus with genetic risk models on the basis of established genome-wide association markers: A systematic review. Am J Epidemiol 2013;178:1197-207. [PUBMED]
5.	Look AHEAD Research Group, Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: Four-year results of the Look AHEAD trial. Arch Intern Med 2010;170:1566-75. [PUBMED]
6.	Zhang X, Ma L, Peng F, Wu Y, Chen Y, Yu L, et al. The endothelial dysfunction in patients with type 2 diabetes mellitus is associated with IL-6 gene promoter polymorphism in Chinese population. Endocrine 2011;40:124-9.
7.	Koch L. Epidemiology: Genetic T2DM risk factor found. Nat Rev Endocrinol 2014;10:128. [PUBMED]
8.	Zia A, Kiani AK, Bhatti A, John P. Genetic susceptibility to type 2 diabetes and implications for therapy. J Diabetes Metab 2013; 4:248-2.
9.	Kwak SH, Park KS. Genetics of type 2 diabetes and potential clinical implications. Arch Pharm Res 2013;36:167-77.
10.	Illig T, Bongardt F, Schöpfer A, Müller-Scholze S, Rathmann W, Koenig W, et al. Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes. J Clin Endocrinol Metab 2004;89:5053-8.
11.	Chua KH, Kee BP, Tan SY, Lian LH. Interleukin-6 promoter polymorphisms (-174 G/C) in Malaysian patients with systemic lupus erythematosus. Braz J Med Biol Res 2009;42:551-5.
12.	Sfrent-Cornateanu R, Mihai C, Balan S, Ionescu R, Moldoveanu E. The IL-6 promoter polymorphism is associated with disease activity and disability in systemic sclerosis. J Cell Mol Med 2006;10:955-9.
13.	Mirowska-Guzel D, Gromadzka G, Mach A, Czlonkowski A, Czlonkowska A. Association of IL1A, IL1B, ILRN, IL6, IL10 and TNF-a polymorphisms with risk and clinical course of multiple sclerosis in a Polish population. J Neuroimmunol 2011;236:87-92.
14.	Karadeniz M, Erdogan M, Berdeli A, Yilmaz C. Association of interleukin-6 -174 G>C promoter polymorphism with increased risk of type 2 diabetes mellitus patients with diabetic nephropathy in Turkey. Genet Test Mol Biomarkers 2014;18:62-5.
15.	Fève B, Bastard JP. The role of interleukins in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol 2009;5:305-11.
16.	Bennermo M, Held C, Stemme S, Ericsson CG, Silveira A, Green F, et al. Genetic predisposition of the interleukin-6 response to inflammation: Implications for a variety of major diseases? Clin Chem 2004;50:2136-40.
17.	Vozarova B, Fernández-Real JM, Knowler WC, Gallart L, Hanson RL, Gruber JD, et al. The interleukin-6 (-174) G/C promoter polymorphism is associated with type-2 diabetes mellitus in Native Americans and Caucasians. Hum Genet 2003;112:409-13.
18.	Fernández-Real JM, Broch M, Vendrell J, Gutiérrez C, Casamitjana R, Pugeat M, et al. Interleukin-6 gene polymorphism and insulin sensitivity. Diabetes 2000;49:517-20.
19.	Klipstein-Grobusch K, Möhlig M, Spranger J, Hoffmann K, Rodrigues FU, Sharma AM, et al. Interleukin-6 g.-174G>C promoter polymorphism is associated with obesity in the EPIC-Potsdam Study. Obesity (Silver Spring) 2006;14:14-8.
20.	Henningsson S, Håkansson A, Westberg L, Baghaei F, Rosmond R, Holm G, et al. Interleukin-6 gene polymorphism -174G/C influences plasma lipid levels in women. Obesity (Silver Spring) 2006;14:1868-73.
21.	Wu W, Wang M, Sun Z, Wang X, Miao J, Zheng Z. The predictive value of TNF-a and IL-6 and the incidence of macrovascular complications in patients with type 2 diabetes. Acta Diabetol 2012;49:3-7.
22.	Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 2002;13:357-68.
23.	Nishimoto N, Kishimoto T. Interleukin 6: From bench to bedside. Nat Clin Pract Rheumatol 2006;2:619-26.
24.	Hamid YH, Rose CS, Urhammer SA, Glümer C, Nolsøe R, Kristiansen OP, et al. Variations of the interleukin-6 promoter are associated with features of the metabolic syndrome in Caucasian Danes. Diabetologia 2005;48:251-60.
25.	Hemmer B, Archelos JJ, Hartung HP. New concepts in the immunopathogenesis of multiple sclerosis. Nat Rev Neurosci 2002;3:291-301.
26.	Nadeem A, Naveed AK, Hussain MM, Aslam M, Siddiqui A, Saeed SA. Variations in association of Interleukin 6-G174C single nucleotide polymorphism with type 2 diabetes mellitus – A review. Int J Diabetes Dev Ctries 2013;33:186-91.
27.	Das SK, Elbein SC. The genetic basis of type 2 diabetes. Cellscience 2006;2:100-131.
28.	Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care 2004;27:813-23.
29.	Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 2011;11:98-107.

Advanced Biomedical Research