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

✍ Scribed by Nabil Mtiraoui; Intissar Ezzidi; Maha Kacem; Manel Ben Hadj Mohamed; Molka Chaieb; Aoutef Bel Haj Jilani; Touhami Mahjoub; Wassim Y. Almawi

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 109 KB
• Volume: 25
• Category: Article
• ISSN: 1520-7552
• DOI: 10.1002/dmrr.892

✦ Synopsis

Abstract

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 ‐592__A__ and ‐819__T__ 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 ‐819__T__ 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, HbA~1c~, 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. Copyright © 2008 John Wiley & Sons, Ltd.