A systematic review and meta analysis of genetic variants and covariates associated with diabetic retinopathy in the Indian population

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Background Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, is a leading cause of blindness worldwide. Conflicting results of association studies that have explored the contribution of genetic and environmental factors in conferring risk toward DR make it difficult to draw a plausible inference, thus necessitating a meta-analysis of all the concerned data on the risk factors documented from India. Methods Meta-analysis (using the R software package) was conducted on the genotype data of 3972 cases (NPDR, i.e., non-proliferative diabetic retinopathy and PDR, i.e., proliferative diabetic retinopathy patients), 3407 controls (Type II diabetic individuals without retinopathy), and covariates from 16 studies from India selected through stringent text-mining from PubMed. Results Two out of 12 SNPs from 6 genes, namely rs833061 of the VEGF gene and rs2070600 of the AGER gene showed nominal association with DR that however, did not hold true after FDR (false discovery rate) correction. Analysis carried out on 20 common covariates from all the selected studies revealed a significant association of 17 clinical covariates with DR. A follow-up global meta-analysis of the associated SNPs revealed a suggestive significant association of rs2070600 with DR in the recessive model. Conclusion No significant association of polymorphic variants even in a meta-analysis among the Indians is probably indicative of the involvement of several rare variants with relatively low impact on DR susceptibility, at least in the Indian context.