Abstract
BackgroundRecent genome-wide association studies have identified multiple loci that are associated with an increased risk of developing coronary artery disease (CAD). The impact of these loci on the disease severity and prognosis of ischemic heart failure due to CAD is currently unknown.MethodsWe undertook association analysis of 7 single nucleotide polymorphism (rs599839, rs17465637, rs2972147, rs6922269, rs1333049, rs501120, and rs17228212) at 7 well established CAD risk loci (1p13.3, 1q41, 2q36.3, 6q25.1, 9p21.3, 10q11.21, and 15q22.33, respectively) in 3,320 subjects diagnosed with systolic heart failure of ischemic aetiology and participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) trial. The primary outcome was the composite of time to first event of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, secondary outcomes included mortality and hospitalization due to worsening heart failure.ResultsNone of the 7 loci were significantly associated with the primary composite endpoint of the CORONA trial (death from cardiovascular cases, nonfatal myocardial infarction, and nonfatal stroke). However, the 1p13.3 locus (rs599839) showed evidence for association with all-cause mortality (after adjustment for covariates; HR 0.74, 95%CI [0.61 to 0.90]; P = 0.0025) and we confirmed the 1p13.3 locus (rs599839) to be associated with lipid parameters (total cholesterol (P = 1.1x10−4), low-density lipoprotein levels (P = 3.5 × 10−7) and apolipoprotein B (P = 2.2 × 10−10)).ConclusionGenetic variants strongly associated with CAD risk are not associated with the severity and outcome of ischemic heart failure. The observed association of the 1p13.3 locus with all-cause mortality requires confirmation in further studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-014-0140-3) contains supplementary material, which is available to authorized users.
Highlights
Recent genome-wide association studies have identified multiple loci that are associated with an increased risk of developing coronary artery disease (CAD)
The earliest findings derived from genome wide association studies were reported by the Wellcome Trust Case Control Consortium (WTCCC) and the German myocardial infarction (MI) Family GWA studies, as well as the Coronary Artery Disease consortium, which together have identified 7 common variants that were robustly associated with CAD [5,7]
With strong prior evidence to be associated with increased CAD risk, are relevant for ischemic Heart Failure (HF) progression as reflected by HF severity and prognosis remains to be determined. We have evaluated these 7 CAD risk loci in ischemic HF patients participating in the COntrolled ROsuvastatin multiNAtional study in heart failure (CORONA) and tested the hypothesis that the SNPs associated with CAD are associated with ischemic HF disease severity and outcome
Summary
Recent genome-wide association studies have identified multiple loci that are associated with an increased risk of developing coronary artery disease (CAD). The impact of these loci on the disease severity and prognosis of ischemic heart failure due to CAD is currently unknown. Mutations in the genes encoding cardiac β-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3) are known to cause hypertrophic and dilated cardiomyopathies [4] These Mendelian diseases only account for a small minority of all HF cases and only explain a minor proportion of the population attributable risk for HF. The earliest findings derived from genome wide association studies were reported by the Wellcome Trust Case Control Consortium (WTCCC) and the German MI Family GWA studies, as well as the Coronary Artery Disease consortium, which together have identified 7 common variants that were robustly associated with CAD [5,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
