title: The -374T/A RAGE polymorphism protects against future cardiac events in nondiabetic patients with coronary artery disease.
abstract: BACKGROUND
  The -374T/A polymorphism of the Receptor for Advanced Glycation End products (RAGE) may exert a protective effect toward the development of atherosclerosis. No data are currently available on the potential prognostic role of this polymorphism in patients with angiographically proven coronary artery disease (CAD). Hereto we sought to address this issue in a large consecutive cohort of patients undergoing coronary revascularization.
  
  
  METHODS
  A total of 643 CAD patients who underwent myocardial revascularization were followed for 4.2 years (interquartile range: 2.2-8.1 years). The rates of major cardiac adverse events (death, nonfatal myocardial infarction, and unstable angina) were compared according to the -374T/A RAGE polymorphism.
  
  
  RESULTS
  During a median follow-up period of 4.2 years, the study endpoint was reached by 126/643 patients (19.6%). We observed adverse cardiac events in 13.4% of patients with AA, 17.5% of those with AT, and 24.2% of those with TT genotype (p <0.05). In univariate Cox proportional hazard analysis, the AA genotype was significantly related to a better outcome in nondiabetic patients (hazard ratio: 0.47, 95% CI: 0.20-0.96; p <0.05). No association was found with adverse events in diabetic subjects. After allowance for potential confounders, the AA genotype remained a significant prognostic factor in the nondiabetic group (adjusted HR: 0.41, 95% CI: 0.17-0.94, p <0.05).
  
  
  CONCLUSIONS
  The -374T/A RAGE polymorphism is an independent protective factor for cardiac events in nondiabetic patients with CAD. The effect of this genetic variant seems to be attenuated in diabetics, who have chronic RAGE upregulation.
authors.affiliation: Department of Cardiology, University Hospital Fondazione IRCCS San Matteo, Pavia, Italy; Interdepartmental Center for Research in Prevention of Cardiovascular and Metabolic Disorders (CIRMC), University of Pavia, Pavia, Italy.
authors.forename: Colomba
authors.initials: C
authors.lastname: Falcone
authors.forename: Diego
authors.initials: D
authors.lastname: Geroldi
authors.forename: Maria P
authors.initials: MP
authors.lastname: Buzzi
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Yilmaz
authors.forename: Jacopo M
authors.initials: JM
authors.lastname: Fontana
authors.forename: Luigi
authors.initials: L
authors.lastname: Vignali
authors.forename: Chiara
authors.initials: C
authors.lastname: Boiocchi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Sbarsi
authors.forename: Mariaclara
authors.initials: M
authors.lastname: Cuccia
mesh_terms: D000225:Adenine / Q000378:metabolism; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics; D017127:Glycation End Products, Advanced / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D013936:Thymidine / Q000235:genetics
chemical_list: D005819:Genetic Markers; D017127:Glycation End Products, Advanced; D000225:Adenine; D013936:Thymidine