Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease.
Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease.
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DOI：
10.1161/circgenetics.108.793158
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发表时间：
2008-12
期刊：
影响因子：
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通讯作者：
Anderson JL
中科院分区：
文献类型：
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作者：
Horne BD;Carlquist JF;Muhlestein JB;Bair TL;Anderson JL
在至少25个独立的人群中，染色体9p21基因座与冠心病(CHD)相关，但已经评估了多种临床上不同的表型。利用冠状动脉造影术(CAD)的表型，本研究评估了9p21单核苷酸多态(SNPs)是否可以预测CAD患者的缺血事件(例如，心肌梗死[MI])。对1994年至2007年接受冠状动脉造影术的患者(人群组1A：N=1,748；组1B：N=1,014)进行了评估，以了解9p21标记单核苷酸多态(rs2383206，A→G)与冠状动脉造影有意义的冠心病患者发生的心肌梗死和死亡事件的相关性。另一种假设在另外两组冠心病和非冠心病患者的血管造影术中评估了rs2383206(组2A：n=2,122；组2B：n=1,466)：普遍的MI与CAD/无MI(以及MI与非CAD和CAD/无MI与非CAD)。未发现rs2383206与Set 1A(OR=0.95每G等位基因，p趋势=0.48)和Set 1B(OR=0.91每G等位基因，p趋势=0.28)的事件，或与Set 2A(OR=0.96每G等位基因，p趋势=0.57)和Set 2B(OR=0.89每G等位基因，p趋势=0.21)的MI/无MI相关。相反，与非冠心病患者相比，rs2383206与冠心病/无心肌梗死相关(SET 2A：P趋势=0.0001；SET 2B：P趋势=0.0008)。染色体9p21基因座与突发事件或流行的心肌梗死无关，尽管它确实可以预测冠心病的诊断。这与9p21与心肌梗死有关的报道相矛盾，可能是由于表型分配的差异。这表明，需要高质量的CAD和MI表型来剖析遗传变异对CHD病理生理学每个阶段的具体贡献。
A chromosome 9p21 locus is associated with coronary heart disease (CHD) in at least 25 independent populations, but multiple clinically-distinct phenotypes have been evaluated. Utilizing angiographic coronary artery disease (CAD) phenotyping, this study evaluated whether 9p21 single nucleotide polymorphisms (SNPs) predict ischemic events (e.g., myocardial infarction [MI]) among CAD patients. Patients undergoing coronary angiography during 1994-2007 (population set 1A: N=1,748; set 1B: N=1,014) were evaluated for association of a 9p21 tagging SNP (rs2383206, A→G) with incident MI and death events among patients with angiographically-significant CAD. Another hypothesis evaluated rs2383206 in two additional angiographic sets of both CAD and non-CAD patients (set 2A: N=2,122; set 2B: N=1,466) for prevalent MI vs. CAD/no MI (and for MI vs. non-CAD and CAD/no MI vs. non-CAD). No association of rs2383206 was found with events in set 1A (OR=0.95 per G allele, p-trend=0.48) and set 1B (OR=0.91 per G allele, p-trend=0.28), or with MI vs. CAD/no MI in set 2A (OR=0.96 per G allele, p-trend=0.57) and set 2B (OR=0.89 per G allele, p-trend=0.21). In contrast, rs2383206 was associated with CAD/no MI compared with non-CAD (set 2A: p-trend=0.0001; set 2B: p-trend=0.0008). The chromosome 9p21 locus was not associated with incident events or prevalent MI, although it did predict CAD diagnosis. This contradicts reports of a 9p21 association with MI, likely due to differences in phenotype assignment. This suggests that high-quality phenotyping for CAD and MI is required to dissect the specific contributions of genetic variation to each stage of CHD pathophysiology.