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

• Published in: Molecular genetics and metabolism Vol. 85; no. 2; pp. 149 - 156
• Main Authors: dos Santos, Kátia Gonçalves, Canani, Luís Henrique, Luiz Gross, Jorge, Tschiedel, Balduíno, Elisabete Pires Souto, Kátia, Roisenberg, Israel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2005
• Subjects: African Continental Ancestry Group - genetics; Aged; Brazil - epidemiology; Brazilians; Case-Control Studies; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - ethnology; Diabetes Mellitus, Type 2 - genetics; Diabetic Nephropathies - ethnology; Diabetic Nephropathies - etiology; Diabetic Nephropathies - genetics; Diabetic nephropathy; Diabetic retinopathy; Diabetic Retinopathy - ethnology; Diabetic Retinopathy - etiology; Diabetic Retinopathy - genetics; European Continental Ancestry Group - genetics; Female; Genetic Linkage; Humans; Ischemic heart disease; Male; Middle Aged; Myocardial Ischemia - ethnology; Myocardial Ischemia - etiology; Myocardial Ischemia - genetics; Polymorphism; Polymorphism, Genetic; Promoter Regions, Genetic; RAGE; Receptor for Advanced Glycation End Products; Receptors, Immunologic - genetics; Risk; Type 2 diabetes; Ischemic heart disease; Type 2 diabetes; Diabetic retinopathy; Diabetic nephropathy; Brazilians; RAGE; Polymorphism
• ISSN: 1096-7192; 1096-7206
• DOI: 10.1016/j.ymgme.2005.02.010

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.