The 9p21 locus is associated with coronary artery disease and cardiovascular events in the presence (but not in the absence) of coronary calcification

PLoS One. 2014 Apr 14;9(4):e94823. doi: 10.1371/journal.pone.0094823. eCollection 2014.

Abstract

Variants at the 9p21 locus have been associated with coronary artery disease (CAD); coronary artery calcification (CAC) is related to CAD and other cardiovascular events. To determine the association of the 9p21 locus with CAD in the presence and absence of CAC, 4 groups were enrolled in a case-control study, including 527 CAD patients without CAC, 692 CAD patients with CAC, 585 individuals with simple CAC but no CAD, and 725 healthy controls. The rs1333049 representing the locus was associated with CAD in the presence of CAC (odds ratio = 1.38 in allelic analysis, 95%CI, 1.19-1.60, P<0.001), but not in the absence of CAC. Additionally, rs1333049 was not associated with simple CAC or CAC severity/extent in CAD patients with CAC. 849 CAD patients undergoing revascularization (660 with CAC and 189 without CAC) were enrolled in a cohort study to test its association with cardiovascular events in CAD patients with and without CAC in a 3-year follow-up. rs1333049 was significantly associated with the incidence of cardiovascular events in non-target vessels in patients with CAC (hazard ratio = 1.44, 95%CI, 1.08-1.91, P = 0.012), but not in those without CAC. The variants at the 9p21 locus were related to CAD and post-revascularization events only in the presence of CAC, suggesting that they may confer risk of calcification-related coronary atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcinosis / complications*
  • Calcinosis / genetics
  • Cardiomyopathies / complications*
  • Cardiomyopathies / genetics
  • Case-Control Studies
  • Chromosomes, Human, Pair 9 / genetics*
  • Coronary Artery Disease / complications*
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / genetics*
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease*
  • Humans
  • Incidence
  • Linear Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Proportional Hazards Models

Grants and funding

The study was supported by NSFC projects 81322002/81270333/31171220, 973 program 2012CB517804, and the Fundamental Research Funds for the Central Universities with grant 2012Y04 to Dr. Wang. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.