title: Age of onset of myocardial infarction: is promoter polymorphism of the RAGE gene implicated?
abstract: Receptor 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.
authors.affiliation: Interdipartimental Center for Research in Molecular Medicine (CIRMC), University of Pavia, Pavia, Italy. chiara.boiocchi@unipv.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Boiocchi
authors.forename: Sara
authors.initials: S
authors.lastname: Bozzini
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Buzzi
authors.forename: Sandra
authors.initials: S
authors.lastname: Schirinzi
authors.forename: Michele
authors.initials: M
authors.lastname: Zorzetto
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pelissero
authors.forename: Mariaclara
authors.initials: M
authors.lastname: Cuccia
authors.forename: Colomba
authors.initials: C
authors.lastname: Falcone
mesh_terms: D017668:Age of Onset; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics*
chemical_list: D000067759:Receptor for Advanced Glycation End Products