Association of the Receptor for Advanced Glycation End Products Gene Polymorphisms with Diabetic Retinopathy in Type 2 Diabetes: a Meta-analysis

Aims: To investigate the association between diabetic retinopathy (DR) in type 2 diabetes mellitus and three polymorphisms of the receptor for advanced glycation end products (RAGE) gene, -429T/C, -374T/A and Gly82Ser.

Methods: A literature search was conducted through PubMed and Web of Science (up to August 31, 2011). Pooled odds ratios (ORs) were estimated using fixed-effects (FE) and random-effects (RE) models in co-dominant, recessive and dominant models. A sensitivity analysis was performed by excluding invalid studies.

Results: Six articles investigated the -429T/C polymorphism, 7 publications were associated with the -374T/A polymorphism and 5 studies were associated with Gly82Ser in DR. For the -429T/C variant, we found no significant difference between DR patients and those with diabetes without retinopathy. A significant association of allele A with DR was found in the recessive model for the -374T/A variant (RE OR = 0.64, 95% CI = 0.42-0.99, p = 0.05, p heterogeneity = 0.55). In the recessive and co-dominant models for the Gly82Ser polymorphism, the pooled ORs were positive in the fixed-effects model (FE OR = 2.89, 95% CI = 1.49-5.60, p = 0.002, p heterogeneity = 0.20; and FE OR = 3.45, 95% CI = 1.76-6.67, p = 0.0003, p heterogeneity = 0.07, respectively), but in the random-effects model the results were negative.

Conclusions: Our research confirmed an association between the RAGE -374T/A polymorphism and retinopathy in subjects with type 2 diabetes and the -374AA allele was found to be a protective factor for type 2 diabetes. Otherwise, the RAGE Gly82Ser polymorphism might be considered a significant risk for DR in Asian populations.