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 s...
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| Published in: | Molecular genetics and metabolism Vol. 85; no. 2; pp. 149 - 156 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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. 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. |
| Author | Canani, Luís Henrique Tschiedel, Balduíno Elisabete Pires Souto, Kátia dos Santos, Kátia Gonçalves Luiz Gross, Jorge Roisenberg, Israel |
| Author_xml | – sequence: 1 givenname: Kátia Gonçalves surname: dos Santos fullname: dos Santos, Kátia Gonçalves organization: Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil – sequence: 2 givenname: Luís Henrique surname: Canani fullname: Canani, Luís Henrique organization: Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil – sequence: 3 givenname: Jorge surname: Luiz Gross fullname: Luiz Gross, Jorge organization: Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil – sequence: 4 givenname: Balduíno surname: Tschiedel fullname: Tschiedel, Balduíno organization: Endocrinology Division, Grupo Hospitalar Conceição, Porto Alegre, RS, Brazil – sequence: 5 givenname: Kátia surname: Elisabete Pires Souto fullname: Elisabete Pires Souto, Kátia organization: Endocrinology Division, Grupo Hospitalar Conceição, Porto Alegre, RS, Brazil – sequence: 6 givenname: Israel surname: Roisenberg fullname: Roisenberg, Israel email: israberg@ufrgs.br organization: Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15896660$$D View this record in MEDLINE/PubMed |
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| Keywords | Ischemic heart disease Type 2 diabetes Diabetic retinopathy Diabetic nephropathy Brazilians RAGE Polymorphism |
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| SubjectTerms | 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 |
| Title | 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 |
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