-374T/A polymorphism of the RAGE gene promoter in relation to severity of coronary atherosclerosis

Background: We have recently reported that homozygosity for the minor A-allele of RAGE (receptor for advanced glycation end products) -374T/A polymorphism may exert a protective effect toward the development of angiographic coronary artery disease (CAD). Here we focused on the putative involvement of this functional RAGE polymorphism on the severity of coronary atherosclerosis as assessed by angiography. Methods: In a total of 234 consecutive Caucasian patients with angiographically proven CAD, the severity of coronary atherosclerosis was assessed by the number of diseased vessels (greater than 50% stenosis). Genotyping for the -374T/A variant was performed by means of PCR-RFLPs. Results: The mean number of diseased vessels was significantly lower in patients with the AA genotype (1.47 +/- 0.68) than in those with the AT or TT genotype (1.88 +/- 0.82, p=0.029). After confounding variables were controlled for, the number of diseased vessels remained significantly different in the AA genotype carriers from that in the AT or TT carriers (p=0.041, ANCOVA). Conclusions: Our data suggest that the RAGE -374T/A polymorphism is one of the likely candidate determinants for the genetic variance of disease phenotype in coronary atherosclerosis. (c) 2004 Elsevier B.V. All rights reserved.