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 63bp 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 63bp 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.
dos Santos
Kátia Gonçalves
KG
Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Canani
Luís Henrique
LH
Gross
Jorge Luiz
JL
Tschiedel
Balduíno
B
Pires Souto
Kátia Elisabete
KE
Roisenberg
Israel
I
D000368:Aged; D044383:Black People / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000208:ethnology / Q000209:etiology / Q000235:genetics; D003930:Diabetic Retinopathy / Q000208:ethnology / Q000209:etiology / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012306:Risk; D044465:White People / Q000235:genetics
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic