A meta-analysis of receptor for advanced glycation end products gene: four well-evaluated polymorphisms with diabetes mellitus.

Genetic association studies on the gene encoding receptor for advanced glycation end products (RAGE) and diabetes mellitus have reported conflicting results. To evaluate the association of RAGE gene four widely-evaluated polymorphisms (T-429C, T-374A, Gly82Ser and G1704T) and diabetes mellitus, a meta-analysis was conducted. A random-effects model was applied irrespective of between-study heterogeneity. There were a total of 5808/3742 (n=14) case-patients/controls (studies) for T-429C, 8259/6935 (n=19) for T-374A, 7029/5266 (n=19) for Gly82Ser, and 2843/3302 (n=13) for G1704T. Overall results detected no significant association of polymorphisms T-429C, T-374A and Gly82Ser with diabetes risk. There was a trend toward an increased risk for alleles 1704T relative to 1704G (odds ratio [OR]=1.09; 95% confidence interval [CI]: 0.98-1.22; I(2)=0). Subgroup analysis by ethnicity indicated that allele 1704T conferred a significantly increased risk in East Asians (OR=1.21; 95% CI: 1.04-1.4; I(2)=0) but not in Caucasians (OR=0.8; 95% CI: 0.6-1.07; I(2)=0), and that by type of diabetes mellitus indicated that association was potentiated exclusively for G1704T with diabetic retinopathy (OR=1.24; 95% CI: 1.01-1.51; I(2)=0). No publication bias was observed. Our results provide convincing evidence regarding the association of RAGE gene 1704T allele with an increased risk of diabetes mellitus, especially diabetic retinopathy. Notably, this effect was more pronounced in East Asians.