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AbstractReceptor for advanced glycation endproducts (RAGE) is a cell-surface molecule member of the immunoglobulin superfamily and engages differing ligands relevant to distinct processes. A growing body of evidence has suggested that RAGE may promote vascular inflammation through several mechanisms. The objective of this study was to identify the possible relationship between the −374 T/A polymorphism of the RAGE gene, myocardial infarction (MI), and its age of onset. A total of 691 MI patients and 234 matched controls were investigated. In this study, the frequency of the A allele and AA genotype of the −374 T/A promoter polymorphism is significantly lower in patients with MI respect to the control group (p< 0.01). Our results showed a significant role of the AA genotype on age of onset of MI. In particular, the mean age of the first MI was higher in patients with the AA genotype as compared to those that were AT or TT genotype carriers (p= 0.002). The relationship between −374 T/A RAGE polymorphism and age for the appearance of MI was independently related to common risk factors of disease (p< 0.01). Kaplan–Meier curves confirmed that subjects with the AA genotype have a later development of MI (p= 0.0022). This study is the first to investigate the role of RAGE polymorphisms on the susceptibility to develop the acute coronary events in the Italian population and identified this polymorphism as an age-related factor for MI development. The homozygous AA genotype may exert a protective role against the early development of MI. [ABSTRACT FROM AUTHOR]

AbstractAdhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leukocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule-1 (PECAM-1), involved in this migration, has been associated with the development of atherosclerosis. Studies have investigated an association between coronary artery disease (CAD) and single-nucleotide polymorphisms (SNPs) located in functionally important domains of the PECAM-1 gene with inconsistent results. Thus, we have analyzed the distribution of V125L, N563S, and G670R SNPs in patients and controls from northern Italy, and also analyzed another functional variant identified in the 5′-untranslated region (UTR) of the PECAM-1 gene (53 G→A). The polymorphisms of PECAM-1 were genotyped by PCR amplification with sequence-specific primers (PCR-SSP) in 119 controls and 431 CAD patients. Our results demonstrate that genotype and allele frequencies for the 53 G/A polymorphism are significantly different in patients affected by CAD compared to healthy controls, whereas, as regards the V125L and N563S polymorphisms, only the allelic frequency is significantly different. We have shown that there were a significant differences for the 53 G/A and V125L and N563S polymorphisms of PECAM-1 in patients affected by CAD compared to controls. This demonstrates a possible involvement of this gene in contributing to the development of CAD. Therefore, an understanding of the role of the PECAM-1 molecule in this complex mechanism is of pivotal significance in further development of innovative and suitable medical therapies in the future. [ABSTRACT FROM AUTHOR]