Horne Benjamin D, Carlquist John F, Muhlestein Joseph B, Bair Tami L, Anderson Jeffrey L
Cardiovascular Department, Intermountain Medical Center, Murray, UT 84157, USA.
Circ Cardiovasc Genet. 2008 Dec;1(2):85-92. doi: 10.1161/CIRCGENETICS.108.793158.
A chromosome 9p21 locus is associated with coronary heart disease in 25 independent populations, but multiple clinically distinct phenotypes have been evaluated. Using angiographic coronary artery disease (CAD) phenotyping, this study evaluated whether 9p21 single-nucleotide polymorphisms predict ischemic events (eg, myocardial infarction [MI]) among CAD patients.
Patients undergoing coronary angiography during 1994 to 2007 (population set 1A: n=1748; set 1B: n=1014) were evaluated for association of a 9p21 tagging single-nucleotide polymorphism (rs2383206, A 224 G) with incident MI and death events among patients with angiographically significant CAD. Another hypothesis evaluated rs2383206 in 2 additional angiographic sets of both CAD and non-CAD patients (set 2A: n=2122; set 2B: n=1466) for prevalent MI versus CAD/no MI (and for MI versus non-CAD and CAD/no MI versus non-CAD). No association of rs2383206 was found with events in set 1A (odds ratio, 0.95 per G allele; P trend=0.48) and set 1B (odds ratio, 0.91 per G allele; P trend=0.28) or with MI versus CAD/no MI in set 2A (odds ratio, 0.96 per G allele; P trend=0.57) and set 2B (odds ratio, 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 because of 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 coronary heart disease pathophysiology.
9号染色体p21位点在25个独立人群中与冠心病相关，但已评估了多种临床不同的表型。本研究采用冠状动脉造影冠心病（CAD）表型分析，评估9p21单核苷酸多态性是否能预测CAD患者中的缺血事件（如心肌梗死[MI]）。
对1994年至2007年期间接受冠状动脉造影的患者（人群集1A：n = 1748；集1B：n = 1014）进行评估，以确定9p21标签单核苷酸多态性（rs2383206，A224G）与冠状动脉造影显示有显著CAD的患者发生MI和死亡事件之间的关联。另一个假设在另外两组CAD和非CAD患者的血管造影组中评估rs2383206（集2A：n = 2122；集2B：n = 1466），以比较现患MI与CAD/无MI（以及MI与非CAD和CAD/无MI与非CAD）。在集1A（每G等位基因优势比为0.95；P趋势 = 0.48）和集1B（每G等位基因优势比为0.91；P趋势 = 0.28）中未发现rs2383206与事件相关，在集2A（每G等位基因优势比为0.96；P趋势 = 0.57）和集2B（每G等位基因优势比为0.89；P趋势 = 0.21）中也未发现rs2383206与MI与CAD/无MI相关。相比之下，与非CAD相比，rs2383206与CAD/无MI相关（集2A：P趋势 = 0.0001；集2B：P趋势 = 0.0008）。
9号染色体p21位点与新发事件或现患MI无关，尽管它确实能预测CAD诊断。这与9p21与MI相关的报道相矛盾，可能是由于表型分类的差异。这表明需要对CAD和MI进行高质量的表型分析，以剖析基因变异对冠心病病理生理各阶段的具体贡献。
