A Common Variant at Chromosome 9P21.3 Is Associated With Age of Onset of Coronary Disease but Not Subsequent Mortality
A Common Variant at Chromosome 9P21.3 Is Associated With Age of Onset of Coronary Disease but Not Subsequent Mortality
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DOI：
10.1161/circgenetics.109.917443
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发表时间：
2010-06-01
影响因子：
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通讯作者：
Cameron, Vicky A.
中科院分区：
文献类型：
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作者：
Ellis, Katrina L.;Pilbrow, Anna P.;Cameron, Vicky A.
背景：染色体9p21.3 （chr9p21.3）最近被一些全基因组关联研究确定为与冠状动脉疾病风险最密切相关的基因组区域。在chr9p21.3位点中，单核苷酸多态性rs1333049已被证明与发生冠状动脉疾病的易感性最密切相关。然而，rs1333049对已确诊冠心病患者临床结局的影响尚不明确。方法和结果：冠状动脉疾病队列研究（CDCS） （n=1054）和心肌梗死后（PMI） （n=816）研究参与者进行rs1333049基因分型。记录了临床病史、循环血脂、神经激素、心功能和出院药物。全因死亡率和心血管疾病住院再入院记录的中位随访期为CDCS组4.0年，PMI组9.1年。高危C等位基因纯合子的CDCS患者发生冠心病（P= 0.005）、心绞痛（P= 0.025）、心肌梗死（P= 0.022）和经皮腔内冠状动脉成形术（P= 0.009）的发病年龄提前2 ~ 5年。CC基因型患者的总胆固醇（P= 0.033）和甘油三酯（P= 0.003）水平也较高。具有CC基因型的PMI参与者在入院时年轻3岁（P= 0.009）。Cox比例风险分析调整了已建立的风险增加预测因子，结果显示rs1333049基因型与CDCS组（P= 0.214）或PMI组（P= 0.696）的死亡率均无显著相关性。结论：在2个冠心病队列中，chr9p21.3多态性rs1333049与较早的发病年龄相关，但与较差的临床预后无关。（中国心血管病杂志，2010;3:286-293）
Background-Chromosome 9p21.3 (chr9p21.3) recently was identified by several genome-wide association studies as the genomic region most strongly associated with the risk of coronary artery disease. Within the chr9p21.3 locus, the single-nucleotide polymorphism rs1333049 has been demonstrated to be most strongly associated with susceptibility to developing coronary artery disease. However, the effect of rs1333049 on clinical outcomes in patients with established coronary disease has yet to be determined.Methods and Results-Coronary Disease Cohort Study (CDCS) (n=1054) and Post-Myocardial Infarction (PMI) (n=816) study participants were genotyped for rs1333049. Clinical history, circulating lipids, neurohormones, cardiac function, and discharge medications were documented. All-cause mortality and cardiovascular hospital readmissions were recorded over a median follow-up period of 4.0 years for the CDCS cohort and 9.1 years for the PMI cohort. The CDCS patients homozygous for the high-risk C allele had an age of onset 2 to 5 years earlier for coronary disease (P=.005), angina (P=.025), myocardial infarction (P=.022), and percutaneous transluminal coronary angioplasty (P=.009). Patients with the CC genotype also had higher levels of total cholesterol (P=.033) and triglycerides (P=.003). The PMI participants with the CC genotype were 3 years younger on admission (P=.009). Cox proportional hazards analysis adjusting for established predictors of increased risk showed no significant association between rs1333049 genotype and mortality in either the CDCS (P=.214) or the PMI (P=.696) cohorts.Conclusions-The chr9p21.3 polymorphism rs1333049 was associated with an earlier age of disease onset in 2 coronary disease cohorts but not with poorer clinical outcome in either cohort. (Circ Cardiovasc Genet. 2010; 3: 286-293.)