ECE2009 Poster Presentations Endocrine tumours and neoplasia (53 abstracts)
1Research Unit of Biology and Genetics of Cancer and Haematological and Autoimmune diseases, Faculty of Pharmacy of Monastir, Monastir University, Monastir, Tunisia; 2Nephrology and Internal Medicine Service, EPS F. Bourguiba of Monastir, Monastir, Tunisia; 3Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.
Background: The IL-10 promoter polymorphisms −1082G/A, −819C/T, and −592C/A have been consistently associated with type 2 diabetes (T2DM). We examined whether these polymorphisms variants are also associated with progression of diabetic nephropathy (DN).
Methods: These promoter variants were genotyped in 917 T2DM patients comprising 515 DN patients and 402 control patients without nephropathy (DWN), together with 748 non-diabetic control subjects. Haplotype analysis and multivariate regression analysis were employed in assessing the contribution of IL-10 haplotypes to DN risk, using genotype, clinical and biochemical profile, and their interactions as predictors of DN.
Results: Carriers of mutant −592A and −819T alleles, and −819T/T, −592A/A, and −819C/T genotypes were more frequent in T2DM. However, the −819C/T genotype appeared to be protective of DN, since lower frequency −819T allele and −819C/T genotype were seen in DN patients. Regression analysis identified −1082G/−819T/−592A (GTA) and −1082G/−819T/−592C (GTC) haplotypes as DN-protective haplotypes. Relative to the −1082G/−819C/−592C haplotype, GTA (P=0.044; odds ratio (OR) =0.54, 95% confidence interval (CI): 0.300.98) and GTC (P=0.045; OR =0.56, 95% CI: 0.310.99) haplotypes were associated with decreased odds ratio OR for DN, after controlling for a number of covariates (age, sex, body mass index (BMI), hypertension, glucose, HbA1c, DN duration, total cholesterol).
Conclusions: Our results indicate that genetic variations at the IL-10 promoter influence the risk of nephropathy in T2DM patients and thus represent a potential DN genetic-susceptibility locus worthy of replication.