Association of matrix metalloproteinase‐2 gene variants with diabetic nephropathy risk

Abstract

BACKGROUND: Diabetic nephropathy is a highly destructive microvascular complication of diabetes. Genetic predisposition is involved in the pathogenesis of diabetic nephropathy, with multiple allelic polymorphisms associated with the development and progression of the disease, thereby increasing the overall risk. To date, no study is available that shows the association of matrix metalloproteinase-2 (MMP-2) gene polymorphisms with diabetic nephropathy risk. Thus, we investigated the potential genetic influence of MMP-2 promoter variants in the development of diabetic nephropathy in type 2 diabetic patients. METHODS: In total, 726 type 2 diabetic patients and 310 healthy controls were included in the study and genotyped for MMP-2, -1306C/T, -790T/G, -1575G/T and -735C/T by real-time PCR. The analysis of the outcomes was performed assuming three genetic models. The threshold for statistical significance was set at 0.05. RESULTS: The results showed that the minor allele frequency of the -790T/G variant was significantly higher in patients with and without nephropathy compared to controls. Furthermore, the distribution analysis revealed a significant association of the -790T/G variant, in all genetic models, with increased risk of diabetic nephropathy that persisted after adjusting for key covariates. No significant associations between MMP-2, -1306C/T, -1575G/T, -735C/T and the risk of diabetic nephropathy were detected. Haplotype analysis identified two risk haplotypes GCGC and GTAC associated with diabetic nephropathy. CONCLUSIONS: The present study is the first to demonstrate the allelic and genotypic association of the MMP-2-790T/G variant and two haplotypes with an increased risk of diabetic nephropathy in a Tunisian population with type 2 diabetes.