OBJECTIVE The Pro12Ala polymorphism of the Peroxisome Proliferator–Activated Receptor-g2 (PPARg2) gene is reported to be associated with diabetes. However, its association with diabetic retinopathy (DR) in Type 2 Diabetes Mellitus (T2DM) has been investigated in numerous epidemiologic studies with controversial results. This meta-analysis aimed to collectively assess the association of the Pro12Ala polymorphism with DR in T2DM.
RESEARCH DESIGN AND METHODS Electronic literature searches were conducted on PubMed, ISI Web of Knowledge, EMBASE and the China National Knowledge Internet. Crude odds ratios (ORs) and 95% Confidence intervals (CIs) were calculated using Fixed Effect Model (FEM). Potential sources of heterogeneity and bias were explored.
RESULTS This meta-analysis included genotype data of 2720 cases with DR and 2450 controls free of DR from 8 eligible publications. The results showed the Ala allele had protective effect on DR in T2DM (OR=0.81; 95% CI: 0.68-0.98, P=0.03). There was no  significant evidence against homogeneity (I²=46%, P_{heterogeneity}=0.07). Sensitivity analysis showed homogeneity after exclusion of one Caucasian study which presented big effect on heterogeneity (I²=1%, P_{heterogeneity}= 0.42), then we found a robust association of Pro12Ala polymorphism with DR in T2DM in the left 7 studies (OR=0.75; 95%CI: 0.62-0.91, P=0.003). The possible ethnic differences in the association of Pro12Ala SNP and DR were demonstrated, a significant association was illustrated in the Caucasian subgroup (OR=0.74; 95% CI: 0.59-0.94, P=0.01), while not found in the Asians (OR=0.77; 95%CI: 0.55-1.07, P=0.12). No publication bias was observed.
CONCLUSIONS This meta-analysis suggested an association between Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala allele had a significant protective effect against DR in T2DM.