The-374A allele of the receptor for advanced glycation end products (RAGE) gene promoter is a protective factor against cardiovascular lesions in type 2 diabetes mellitus patients

Background: Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been associated with diabetes, coronary artery disease (CAD) and inflammatory processes. The -374T > A RAGE gene promoter polymorphism was shown to affect gene transcription. The aim of this study was to evaluate the association of the -374T > A polymorphism with the severity of CAD in patients with or without type 2 diabetes mellitus. Methods: We studied 246 Euro-Brazilians with angio-graphically defined CAD (stenosis > 50%), comprising type 2 diabetic (n=98) and non-diabetic subjects (n=148). Genotyping was performed by PCR-restriction fragment length polymorphism using Tsp5091 restriction enzyme. Results: The AA genotype was associated with a significant decrease in CAD severity estimated by the number of diseased vessels (1.43 +/- 0.5 vs. 2.49 +/- 1.1; p=0.002) and the Duke score (27.3 +/- 10.8 vs. 49.3 +/- 20.1; p=0.001) only in the group of CAD subjects with type 2 diabetes mellitus. The protective effect of the AA genotype against severity of CAD was not observed in the non-diabetic group. Conclusion: This result confirms that the -374AA genotype of the RAGE gene promoter is a protective factor against the severity of CAD lesions in type 2 diabetic patients.