Association of VEGF-1499C→T polymorphism with diabetic nephropathy in type 1 diabetes mellitus

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• 作者：Amy-Jayne McKnight ; A. Peter Maxwell ; Chris C. Patterson ; Hugh R. Brady ; David A. Savage
• 关键词：Association ; Nephropathy ; SNP ; Type 1 diabetes ; VEGF
• 刊名：Journal of Diabetes and its Complications
• 出版年：2007
• 出版时间：July-August 2007
• 年：2007
• 卷：21
• 期：4
• 页码：242-245
• 全文大小：88 K

文摘

Vascular endothelial growth factor (VEGF) is reported to be implicated in the development of diabetic nephropathy. We performed a case-control study to determine if VEGF-2578C→A, VEGF-1499C→T, and VEGF-635G→C single-nucleotide polymorphisms (SNPs) in the VEGF gene are associated with predisposition to diabetic nephropathy in type 1 diabetes. Genomic DNA was obtained from Irish type 1 diabetic individuals with nephropathy (cases, n=242) and those without nephropathy (controls, n=301), in addition to 400 healthy control samples. These samples were genotyped for the three SNPs using TaqMan or Pyrosequencing technology. Chi-squared analyses revealed no significant differences in genotype or allele frequencies in cases versus controls for VEGF-2578C→A (genotype, P=.58; allele, P=.52) and VEGF-635G→C (genotype, P=.58; allele, P=.33). However, a positive association with diabetic nephropathy was observed for the VEGF-1499T allele in the Northern Ireland population (P <.001) and subsequently replicated in a separate population from the Republic of Ireland (P <.001; combined, P <.001). Carriage of the VEGF-1499T allele was associated with a twofold excess risk of developing diabetic nephropathy (OR=2.24, 95 % CI=1.50–3.36, P <.0001). No significant differences were found between the healthy control population and the type 1 diabetic population.

Our results suggest that the VEGF-1499T allele, or an allele in linkage disequilibrium with this allele, is associated with susceptibility to diabetic nephropathy in the Irish population.