Abdullah K G, Li L, Shen G-Q, Hu Y, Yang Y, MacKinlay K G, Topol E J, Wang Q K
Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio 44195, USA.
Ann Hum Genet. 2008 Sep;72(Pt 5):654-7. doi: 10.1111/j.1469-1809.2008.00454.x. Epub 2008 May 26.
Genome-wide association studies have separately identified four single nucleotide polymorphisms (SNPs) on chromosome 9p21 that confer susceptibility to coronary artery disease (CAD) and myocardial infarction (MI). This study presents the first analysis of these SNPs (rs10757274, rs2383206, rs2383207, and rs10757278) in a premature, familial CAD/MI population (GeneQuest). We performed a case-control analysis of the GeneQuest Caucasian population with 310 cases with premature CAD and MI (average age at onset of 40.3 +/- 5.1) and 560 non-CAD controls to determine if these SNPs are associated with risk of CAD using both the population-based and family-based association study designs. The four SNPs are significantly associated with premature and familial MI and CAD in the GeneQuest Caucasian population (allelic P= 6.61 x 10(-7) to 1.87 x 10(-8)). Sib-TDT analysis showed that three of the four SNPs could confer significant susceptibility to premature CAD and MI. These results indicate that the four SNPs on chromosome 9p21 are also associated with premature, familial CAD.
全基因组关联研究已分别在9号染色体p21区域鉴定出四个单核苷酸多态性（SNP），这些多态性会增加患冠状动脉疾病（CAD）和心肌梗死（MI）的易感性。本研究首次对一个早发性、家族性CAD/MI人群（GeneQuest）中的这些SNP（rs10757274、rs2383206、rs2383207和rs10757278）进行了分析。我们对GeneQuest白种人群进行了病例对照分析，其中包括310例早发性CAD和MI患者（发病平均年龄为40.3±5.1岁）以及560名非CAD对照者，采用基于人群和基于家系的关联研究设计来确定这些SNP是否与CAD风险相关。在GeneQuest白种人群中，这四个SNP与早发性和家族性MI及CAD显著相关（等位基因P = 6.61×10^(-7)至1.87×10^(-8)）。同胞传递不平衡检验（Sib-TDT）分析表明，四个SNP中的三个可导致对早发性CAD和MI的显著易感性。这些结果表明，9号染色体p21区域的这四个SNP也与早发性、家族性CAD相关。
