The −374A allele of the receptor for advanced glycation end products gene is associated with a decreased risk of ischemic heart disease in African-Brazilians with type 2 diabetes

Three functional polymorphisms described in the promoter of receptor for advanced glycation end products (RAGE) gene were shown to have a marked effect on transcriptional activity. The few studies which analyzed the relationship between these three polymorphisms and the diabetic complications have shown conflicting results. In this case-control study, we evaluated the association between the −429T>C, the −374T>A and the 63 bp insertion/deletion (I/D) polymorphisms in the RAGE gene, and the presence of diabetic retinopathy, diabetic nephropathy and ischemic heart disease, in 703 Brazilians with type 2 diabetes (520 Caucasian- and 183 African-Brazilians). Patients underwent a clinical and laboratory evaluation consisting of a questionnaire, physical examination, assessment of diabetic complications and blood collection. Genotype analysis was performed using the polymerase chain reaction and allele-specific restriction. Logistic regression analyses were used to examine associations between the clinical and genetic variables and the presence of diabetic complications. No association between the −429C, the −374A and the 63 bp D alleles and diabetic retinopathy, diabetic nephropathy or ischemic heart disease was observed in Caucasian-Brazilians with type 2 diabetes. However, the −374A allele was associated with a decreased risk of having ischemic heart disease in African-Brazilian type 2 diabetic patients [odds ratio (OR) = 0.35; 95% confidence interval (CI) = 0.15-0.81; P = 0.014], independently of other risk factors associated with this complication. Thus, our results show that the −374A allele (−374T>A polymorphism) in the RAGE gene is related to the susceptibility of developing ischemic heart disease in African-Brazilians with type 2 diabetes.