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 angiographically 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 Tsp509I 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.


CONCLUSIONS
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.
Picheth
Geraldo
G
Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil. gpicheth@ufpr.br
Costantini
Costantino O
CO
Pedrosa
Fábio O
FO
Leme da Rocha Martinez
Tania
T
Maltempi de Souza
Emanuel
E
D000368:Aged; D000483:Alleles; D001938:Brazil; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012307:Risk Factors
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic