Abstract
BackgroundThe 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.MethodsPublished 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.ResultsA 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.ConclusionsOur meta-analysis confirmed the significant association between rs699947 polymorphism and DR after exclusion of outliers, and rs2010963 polymorphism might be not associated with DR.
Highlights
The vascular endothelial growth factor (VEGFA) gene has been suggested to play an important role in the pathogenesis of diabetic retinopathy (DR)
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
Summary
The vascular endothelial growth factor (VEGFA) gene has been suggested to play an important role in the pathogenesis of diabetic retinopathy (DR). We performed a meta-analysis to clarify the associations between VEGFA polymorphisms and DR risk. It is well established that DR is determined by both genetic and environmental factors. The longer duration of diabetes, poorer control of blood glucose and elevated blood pressure are the major risk factors in the development of DR. Genetic factors play important roles in the pathogenesis of DR [2]. It would be useful to identify molecular markers that may help to predict the development of DR at earlier stages of diabetes. Vascular endothelial growth factor (VEGFA), an endothelial cellspecific mitogen, has been implicated as a major contributor to the development of DR [3]. The VEGFA gene is located on chromosome 6p21.3 and consists of
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