Abstract 16925: Chromosome 9p21 SNPs Haplotypes are Associated with Cardiovascular Outcomes in Patients with Coronary Artery Disease
Introduction: While numerous SNPs in Chromosome 9p21 have been associated with coronary artery disease (CAD) and MI in Caucasians, there are limited and conflicting reports on the association of this locus with prognosis in Caucasians with existing CAD and no reports in blacks or Hispanics.
Hypothesis: We assessed the hypothesis that the 9p21 polymorphisms are associated with increased risk for adverse cardiovascular outcomes in patients with documented CAD.
Methods: We studied the association of 153 chromosome 9p21 SNPs with adverse outcomes among hypertensive CAD patients of multiple race/ethnicity in a case-control sample from INVEST (the INternational VErapamil SR Trandolapril STudy, n= 1460) and replicated findings for 2 SNPs in Caucasians the INFORM (INvestigation oF Outcomes from acute coronary syndromes; n=568) study of acute coronary syndromes (ACS) patients. Adverse outcomes were first occurrence of all cause mortality, nonfatal MI or nonfatal stroke (INVEST) and all cause mortality or cardiac rehospitalization (INFORM). Logistic regression was used for INVEST to calculate the adjusted odds ratios (OR) and 95% confidence interval (CI). Cox regression was used for INFORM to calculate the adjusted hazard ratio (HR) and 95% CI.
Results: In INVEST, haplotypes of 2 distinct linkage disequilibrium (LD) blocks were associated with prognosis. The haplotype comprised of the risk allele for the 5 most often reported 9p21 SNPs: rs10757274 (G), rs2891168 (G), rs2383207 (G), rs10757278 (G) and rs1333049 (C) was paradoxically associated with better prognosis in INVEST Caucasians (OR, 95% CI: 0.72, 0.57-0.92, p = 0.0076) but not blacks (1.21, 0.68-1.24, p = 0.52). This finding was replicated in 2 SNPs in INFORM Caucasians: HR, 95% CI: 0.81, 0.61-1.03 (p = 0.09) for rs2383207 and 0.75, 0.58-0.96 (p = 0.02) for rs10757278. In contrast, a less commonly reported LD block was associated with worse prognosis in INVEST among both Caucasians (OR=1.53 (1.20-1.97), p = 0.0007) and blacks (OR = 4.74 (1.75-12.86), p = 0.002).
Conclusions: A 9p21 polymorphisms haplotype in a different LD block than the most often reported block was associated with worse prognosis among both Caucasians and blacks with prior CAD or ACS. Further confirmation of these findings is warranted.
- © 2010 by American Heart Association, Inc.