Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.
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DOI：
10.1016/s0140-6736(10)61996-4
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发表时间：
2011-01-29
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影响因子：
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通讯作者：
Rader DJ
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作者：
Reilly MP;Li M;He J;Ferguson JF;Stylianou IM;Mehta NN;Burnett MS;Devaney JM;Knouff CW;Thompson JR;Horne BD;Stewart AF;Assimes TL;Wild PS;Allayee H;Nitschke PL;Patel RS;Myocardial Infarction Genetics Consortium;Wellcome Trust Case Control Consortium;Martinelli N;Girelli D;Quyyumi AA;Anderson JL;Erdmann J;Hall AS;Schunkert H;Quertermous T;Blankenberg S;Hazen SL;Roberts R;Kathiresan S;Samani NJ;Epstein SE;Rader DJ
我们测试了遗传因素是否明显有助于冠状动脉粥样硬化的发展，特别是对现有冠状动脉粥样硬化的心肌梗死。我们做了两个全基因组关联研究（GWAS）与冠状动脉造影表型在欧洲血统的参与者。为了确定易患冠状动脉造影疾病（CAD）的基因座，我们比较了患有这种疾病的个体（n= 12,393）和没有这种疾病的个体（n= 7383）。为了确定易患心肌梗死的基因位点，我们将血管造影冠心病合并心肌梗死的患者（n=5783）与血管造影冠心病但无心肌梗死的患者（n=3644）进行了比较。在血管造影CAD患者与对照组的比较中，我们发现了一个新的基因位点ADAMTS7 （p=4·98×10−13）。在合并心肌梗死的冠心病血管造影患者与没有心肌梗死的冠心病血管造影患者的比较中，我们在ABO位点发现了一种新的关联（p=7·62×10−9）。ABO关联归因于糖转移酶缺陷酶，该酶编码ABO血型O表型，先前提出可预防心肌梗死。我们的研究结果表明，特定的遗传易感性促进冠状动脉粥样硬化的发展，而其他易感性在冠状动脉粥样硬化存在时导致心肌梗死。与特定CAD表型的关系可能会改变新基因座在个性化风险评估中的应用，并用于CAD新疗法的开发。PennCath和MedStar的研究得到了宾夕法尼亚大学心血管研究所、华盛顿医院中心MedStar健康研究所和葛兰素史克公司的研究资助。其他研究小组对论文的资助和支持情况在网络附录中有详细说明。
We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12 393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10−13). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10−9). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.