Predictive value of interleukin-10 promoter genotypes and haplotypes in determining the susceptibility to nephropathy in type 2 diabetes patients

Nabil Mtiraoui; Intissar Ezzidi; Molka Chieb; Maha Kacem; Touhami Mahjoub; WassimY Almawi

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Endocrine Abstracts (2009) 20 P178

ECE2009 Poster Presentations Endocrine tumours and neoplasia (53 abstracts)

Predictive value of interleukin-10 promoter genotypes and haplotypes in determining the susceptibility to nephropathy in type 2 diabetes patients

Nabil Mtiraoui ¹ , Intissar Ezzidi ¹ , Molka Chieb ² , Maha Kacem ² , Touhami Mahjoub ² & WassimY Almawi ¹

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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): 0.30–0.98) and GTC (P=0.045; OR =0.56, 95% CI: 0.31–0.99) 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.