Ellis Katrina L, Frampton Chris M, Pilbrow Anna P, Troughton Richard W, Doughty Rob N, Whalley Gillian A, Ellis Chris J, Skelton Lorraine, Thomson Judith, Yandle Tim G, Richards A Mark, Cameron Vicky A
Christchurch Cardioendocrine Research Group, Department of Medicine, University of Otago-Christchurch, Christchurch, New Zealand.
Circ Cardiovasc Genet. 2011 Dec;4(6):636-46. doi: 10.1161/CIRCGENETICS.111.960336. Epub 2011 Oct 7.
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.
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).
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.
全基因组关联研究已鉴定出与冠状动脉疾病风险相关的基因变异；然而，它们是否影响疾病进展在很大程度上尚不清楚。本研究调查了1p13.3（rs599839）、1q41（rs17465637）和3q22.3（rs9818870）位点的多态性与健康志愿者和已确诊心脏病患者心血管结局之间的关联。
对来自坎特伯雷健康志愿者研究（HV）（n = 1649）、冠状动脉疾病队列研究（CDCS）（n = 1797）和心肌梗死后研究（PMI）（n = 906）（新西兰）的参与者进行rs599839、rs9818870和rs17465637基因分型。在中长期随访（HV中位数为5.9年；CDCS为3.7年；PMI为11.3年）期间，测试了基因型与人体测量特征、神经激素分析、超声心动图和临床结局之间的关联。在1p13.3位点，与携带AA基因型的参与者相比，携带1个或更多rs599839 G等位基因的HV和CDCS参与者血脂异常患病率较低（P≤0.005），或低密度脂蛋白水平较低（P = 0.031）、总胆固醇水平较低（P = 0.004），和/或心肌梗死病史较少（P≤0.04）。此外，超声心动图显示CDCS和PMI中AG/GG基因型参与者心脏功能更好（P≤0.026），且随访期间因非ST段抬高型心肌梗死再次入院的CDCS中AG/GG基因型参与者较少（P = 0.012）。1q41（rs17465637）位点的多态性与HV队列（P = 0.028）和PMI队列（P = 0.008）中更好的心血管结局相关，3q22.3（rs9818870）是HV队列中死亡/入院的预测因子（P = 0.045）。
这些数据表明，1p13.3和1q41位点的冠状动脉疾病基因组风险变异与心脏病患者随后的临床结局相关，并证实3q22.3位点的rs9818870是无明显心脏病个体心血管风险的预测因子。
