Meta-analysis of association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ2 gene and diabetic retinopathy in Caucasians and Asians

Purpose: The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma 2 (PPAR gamma 2) gene is reported to be associated with diabetes. However, the gene's 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. Methods: An electronic literature search was conducted on PubMed, ISI Web of Knowledge, EMBASE, and the China National Knowledge Internet. A dominant model [(Pro/Ala + Ala/Ala) versus Pro/Pro] was used to ensure adequate statistical power. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effect model. Potential sources of heterogeneity and bias were explored. Results: This meta-analysis included genotype data from 2,720 cases with DR and 2,450 controls free of DR from eight eligible publications. The results showed the Ala allele had a 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 (I-2=46%, P-heterogeneity=0.07). The sensitivity analysis showed a robust association of the Pro12Ala polymorphism with DR in T2DM after a study involving Caucasians that presented a big effect on heterogeneity (OR=0.75; 95% CI: 0.62-0.91, p=0.003) was excluded. Possible ethnic differences in the association of the Pro12Ala single nucleotide polymorphism 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) but was not found in the Asian subgroup (OR=0.77; 95% CI: 0.55-1.07, p=0.12). No publication bias was observed. Conclusions: This meta-analysis suggested a significant association exists between the Pro12Ala polymorphism and DR in T2DM with ethnic differences. The Ala allele had a significant protective effect against DR in T2DM.