title: Higher incidence of death in multi-vessel coronary artery disease patients associated with polymorphisms in chromosome 9p21.
abstract: BACKGROUND
  We investigated whether 9p21 polymorphisms are associated with cardiovascular events in a group of 611 patients enrolled in the Medical, Angioplasty or Surgery Study II (MASS II), a randomized trial comparing treatments for patients with coronary artery disease (CAD) and preserved left ventricular function.
  
  
  METHODS
  The participants of the MASS II were genotyped for 9p21 polymorphisms (rs10757274, rs2383206, rs10757278 and rs1333049). Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, death from cardiac causes and myocardial infarction using a Cox proportional hazards survival model.
  
  
  RESULTS
  We observed significant differences between patients within each polymorphism genotype group for baseline characteristics. The frequency of diabetes was lower in patients carrying GG genotype for rs10757274, rs2383206 and rs10757278 (29.4%, 32.8%, 32.0%) compared to patients carrying AA or AG genotypes (49.1% and 39.2%, p = 0.01; 52.4% and 40.1%, p = 0.01; 47.8% and 37.9%, p = 0.04; respectively). Significant differences in genotype frequencies between double and triple vessel disease patients were observed for the rs10757274, rs10757278 and rs1333049. Finally, there was a higher incidence of overall mortality in patients with the GG genotype for rs2383206 compared to patients with AA and AG genotypes (19.5%, 11.9%, 11.0%, respectively; p = 0.04). Moreover, the rs2383206 was still significantly associated with a 1.75-fold increased risk of overall mortality (p = 0.02) even after adjustment of a Cox multivariate model for age, previous myocardial infarction, diabetes, smoking and type of coronary anatomy.
  
  
  CONCLUSIONS
  Our data are in accordance to previous evidence that chromosome 9p21 genetic variation may constitute a genetic modulator in the cardiovascular system in different scenarios. In patients with established CAD, we observed an association between the rs2383206 and higher incidence of overall mortality and death from cardiac causes in patients with multi-vessel CAD.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute, Sao Paulo University Medical School, Av, Dr, Enéas de Carvalho Aguiar, 44 Cerqueira César, Sao Paulo, SP, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Gioli-Pereira
authors.forename: Paulo Caleb Junior Lima
authors.initials: PC
authors.lastname: Santos
authors.forename: Noely Evangelista
authors.initials: NE
authors.lastname: Ferreira
authors.forename: Whady Armindo
authors.initials: WA
authors.lastname: Hueb
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000368:Aged; D001938:Brazil / Q000453:epidemiology; D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use; D016009:Chi-Square Distribution; D002899:Chromosomes, Human, Pair 9; D015897:Comorbidity; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000401:mortality; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000401:mortality; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left
chemical_list: D002317:Cardiovascular Agents