Vascular Endothelial Growth Factor-A (Vegfa) Gene Polymorphisms and Genetic Predisposition of Retinopathy in Type 2 Diabetes Patients of India

摘要

Purpose: Vascular Endothelial Growth Factor - A (VEGFA) promotes angiogenesis and its role in the pathology ofdiabetic retinopathy (DR) is well documented. Although the polymorphisms in VEGFA gene have been shown toincrease the risk of DR development and progression in various ethnicities, few studies have been carried out targetingthe intronic SNPs. Therefore, the main purpose of present study was to assess the genetic predisposition of DR andproliferative DR (PDR) attributed by three intronic polymorphisms of VEGFA gene among type 2 diabetes (T2D)patients.Method: We enrolled total 351 unrelated individuals [93 healthy controls (HC), 110 T2D patients without retinopathy(DWR) and 148 T2D patients with retinopathy (DR)] from the western region of India. Genotyping of rs833069,rs2146323, and rs3025021 SNPs was performed by PCR-RFLP.Results: The AA genotype in a co-dominant model and minor allele (A) of rs2146323 was significantly high in PDRpatients when compared to DWR patients (p = 0.003 and p = 0.010, respectively). However, the SNP was notsignificantly associated with DR when compared to HC or DWR individuals on applying multivariate logisticregression (p = 0.142 and p = 0.045, correspondingly). We did not observe significant variation in the distribution ofrs833069 and rs3025021 polymorphisms among the study groups. Our data suggested rs833069 and rs2146323 SNPswere in linkage disequilibrium (D’=0.947), and ACC of the observed haplotypes showed a significant inverseassociation with PDR (p = 0.001).Conclusion: Our study suggested that minor homozygous genotype of rs2146323 conferred two-fold risk to developPDR in the targeted Indian ethnicity. Further studies in larger population would help in confirming the associationsubstantially.