Interleukin-10–592C/A, –819C/T and –1082A/G promoter variants affect the susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients |
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Authors: | Ezzidi Intissar Mtiraoui Nabil Kacem Maha Mallat Samir G Mohamed Manel Ben Hadj Chaieb Molka Mahjoub Touhami Almawi Wassim Y |
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Institution: | Research unit of Biology and Genetics of Cancer and Haematological and Autoimmune diseases, Faculty of Pharmacy of Monastir, Monastir University, Monastir, Tunisia;, Nephrology and Internal Medicine Service –EPS F. Bourguiba, Monastir, Tunisia;, Nephrology Department, St. Joseph University, Beirut, Lebanon;and Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain |
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Abstract: | Background The Interleukin (IL)-10 polymorphic variants –1082G/A, –819C/T and –592C/A were linked with obesity, metabolic syndrome, and type 2 diabetes (T2DM). We investigated the hypothesis that IL-10 promoter polymorphisms may be associated with the progression of diabetic nephropathy (DN). Design Case-controlled study. Patients Study subjects comprised of 515 DN patients, and 402 normoalbuminuric (DWN) T2DM patients. Measurements IL-10 genotyping was done by PCR-based assays, and the contributions of the IL-10 polymorphic variants to DN were analysed by haplotype analysis and multivariate regression analysis. Results Decreased prevalence of (mutant) –819T allele and –819C/T genotype was seen in DN patients; neither the –1082G/A nor the –592C/A polymorphism was associated with DN. Three-loci haplotype (–1082GA/–819CT/–592CA) analysis identified GTC as DN-protective haplotype. Multivariate regression analysis confirmed the association of GTC haplotype ( P = 0·045; O R = 0·56, 95% CI: 0·31–0·99), and in addition identified GTA haplotype ( P = 0·044; O R = 0·54, 95% CI: 0·30–0·98) as independent predictors of DN after controlling for a number of covariates (age, sex, BMI; hypertension, glucose, HbA1c, DN duration, total cholesterol, medications). Conclusion This study suggests that IL-10 promoter polymorphism influence the risk of nephropathy in Tunisian T2DM patients. |
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