Interleukin-10-592C/A,-819C/T and-1082A/G promoter variants affect the susceptibility to nephropathy in Tunisian type 2 diabetes (T2DM) patients

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). Case-controlled study. Study subjects comprised of 515 DN patients, and 402 normoalbuminuric (DWN) T2DM patients. 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. 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; OR = 0.56, 95% CI: 0.31-0.99), and in addition identified GTA haplotype (P = 0.044; OR = 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). This study suggests that IL-10 promoter polymorphism influence the risk of nephropathy in Tunisian T2DM patients.