Two polymorphisms (rs699947, rs2010963) in the VEGFA gene and diabetic retinopathy: an updated meta-analysis

BACKGROUND: The vascular endothelial growth factor (VEGFA) gene has been suggested to play an important role in the pathogenesis of diabetic retinopathy (DR). However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the associations between VEGFA polymorphisms and DR risk. METHODS: Published literature from PubMed, EMBASE, Web of Science and Google Scholar were retrieved. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed- or random-effects model. RESULTS: A total of eight studies (1204 cases and 1198 controls) for rs699947 polymorphism and ten studies (1666 cases and 1782 controls) for rs2010963 polymorphism were included in the meta-analysis. The results suggested that rs699947 polymorphism was marginally associated with DR under a homogeneous co-dominant model (AA vs. CC: OR = 1.69, 95% CI = 1.03-2.77, p = 0.040) and a dominant model (AA + AC vs. CC: OR = 1.38, 95% CI = 1.01-1.90, p = 0.040), whereas the association between rs2010963 polymorphism and DR was not significant under all genetic models (all p > 0.05). In the subgroup analysis, the effect size for rs699947 polymorphism was only marginally significant among European populations under a dominant model (OR = 1.47, 95% CI = 1.07–2.02, p = 0.018), but not among East Asians. After exclusion of outliers which were the source of between-study heterogeneity, there was significant association between rs699947 polymorphism and DR under a homogeneous co-dominant model (OR = 1.64, 95% CI = 1.18-2.28, p = 0.003), even after multiple comparison correction. CONCLUSIONS: Our meta-analysis confirmed the significant association between rs699947 polymorphism and DR after exclusion of outliers, and rs2010963 polymorphism might be not associated with DR.