Genomic risk variants at 1p13.3, 1q41, and 3q22.3 are associated with subsequent cardiovascular outcomes in healthy controls and in established coronary artery disease.

Background: Genome-wide association studies have identified gene variants associated with coronary artery disease risk; however, whether they affect disease progression is largely unknown. This study investigated associations between polymorphisms at 1p13.3 (rs599839), 1q41 (rs17465637), and 3q22.3 (rs9818870) and cardiovascular outcomes in healthy volunteers and in patients with established heart disease.

Methods And Results: Canterbury Healthy Volunteer study (HV) (n=1649), Coronary Disease Cohort Study (CDCS) (n=1797), and Post-Myocardial Infarction study (PMI) (n=906) participants (New Zealand), were genotyped for rs599839, rs9818870, and rs17465637. Associations between genotype and anthropometric characteristics, neurohormonal analysis, echocardiography, and clinical outcomes over medium-long-term follow-up (median HV, 5.9 years; CDCS, 3.7 years; PMI, 11.3 years) were tested. At 1p13.3, HV and CDCS participants carrying 1 or more rs599839 G allele had a lower prevalence of dyslipidemia (P ≤ 0.005) or lower levels of low-density lipoprotein (P=0.031) and total (P=0.004) cholesterol and/or less history of myocardial infarction (P ≤ 0.04) compared with AA participants. Moreover, CDCS and PMI AG/GG participants had better cardiac function as indicated by echocardiography (P ≤ 0.026), and fewer CDCS AG/GG participants were readmitted for a non-ST-segment elevation MI (P=0.012) during follow-up. The polymorphism at 1q41 (rs17465637) was associated with better cardiovascular outcomes in the HV (P=0.028) and PMI (P=0.008) cohorts, and 3q22.3 (rs9818870) was a predictor of death/admission in the HV cohort (P=0.045).

Conclusions: These data suggest that coronary artery disease genomic risk variants at 1p13.3 and 1q41 are associated with subsequent clinical outcome in heart patients and confirm rs9818870 at 3q22.3 as a predictor of cardiovascular risk in individuals free of overt heart disease.