In search of association between the VEGF gene polymorphisms: rs3025035, rs3025021, rs2010963 and proliferative diabetic retinopathy in Mexican population.

Abstract

Purpose: Diabetic retinopathy (DR) is classified into non-proliferative DR (NPDR) and proliferative DR (PDR). Without an early screening and effective diagnosis, patients with PDR have an increased risk of the development of serious complications. Vascular Endothelial Growth Factor (VEGF) remains as the main promoter of neovascularization processes, increased vascular permeability and leakage in diabetic retinopathy. Several studies have shown that susceptibility to DR also has a heritable component, independent of glycemic control and duration of diabetes. The Single nucleotide polymorphisms (SNPs) included in this study, rs3025035, rs3025021 and rs2010963, have been associated to PDR in other populations. The aim of this study is to determine whether these SNPs in the VEGF gene are associated with PDR in type 2 diabetic Mexican Population.

Methods: A case-control study was conducted in which 210 individuals were enrolled; 105 individuals with type 2 diabetes with proliferative diabetic retinopathy (PDR) and 105 individuals with type 2 diabetes with non-proliferative retinopathy (NPDR) all which were genotyped for the SNPs previously mentioned; rs3025035, rs3025021 and rs2010963 by qPCR (TaqMan SNP Genotyping Assay). Haplotype and linkage disequilibrium between SNPs were determined. Differences between categorical variables were analyzed by Fisher's exact test, and the analysis of variance (ANOVA) for continuous variables. P values <0.05 were considered to be statistically significant.

Results: One-sided Fisher’s exact test for rs3025021 (OR [95% CI] = 2.9 [2.75, 4.75], P=0.034); rs3025035 (OR [95% CI] = 0.62 [0.15, 2.52], P=0.381) and rs2010963 (OR [95% CI] = 0.86 [0.35,2.13], P=0.466). The Minor allelic frequencies (MAF) obtained were as follows: 30.0% rs3025021, 5.0% rs3025035 and 35% for rs2010963.

Conclusions: The analyses performed showed statistical significant association between rs3025021 and PDR; to our knowledge is the first confirmed association of a polimorphism of the VEGF gene in mexican population . Aditionally; no significant association between rs2010963 and rs3025035 SNPs with PDR was found. Analyses of a larger sample size will demonstrate whether there is a positive association between rs3025035 and rs2010963 and PDR in Mexican population.