AJH：冠状动脉疾病的遗传标志物

近日，明尼苏达大学公共卫生研究学院大学发表论文称他们发现了两个冠状动脉疾病（CAD）的遗传标志物，有助于预示罹患该疾病的风险。

这项研究由明尼苏达州公立学校流行病学和社区卫生助理教授Weihong Tang率领研究，相关研究论文发表在American Journal of Human Genetics杂志上。

Tang表示：我们的研究主要针对两个临床常见的血液测试中的不足之处，即APTT试验和PT测试。我们的目标是要看看是否有遗传标记或在测试过程中存在较高信号分子预示患者患冠状动脉疾病的风险，我们发现在我们的样本中确实有一些着遗传标记物会增加该疾病的患病风险。

Tang的这项研究只关注于美国白人，但她和她的同事们想将范围扩大到包括更多患者在内的群体。她希望开展一个更大的研究将确定遗传与冠心病危险因素之间的联系。

Tang说：目前，我们还有很多工作尚待完成，但我们的研究结果证实这样一个新的测试类型将有助于医生及早发现和治疗凝血疾病。

doi:10.1016/j.ajhg.2012.05.009
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Genetic Associations for Activated Partial Thromboplastin Time and Prothrombin Time, their Gene Expression Profiles, and Risk of Coronary Artery Disease

Weihong Tang, Christine Schwienbacher, Lorna M. Lopez, Yoav Ben-Shlomo6, Tiphaine Oudot-Mellakh7, Andrew D. Johnson8, 9, 10, Nilesh J. Samani1,et al.

Activated partial thromboplastin time (aPTT) and prothrombin time (PT) are clinical tests commonly used to screen for coagulation-factor deficiencies. One genome-wide association study (GWAS) has been reported previously for aPTT, but no GWAS has been reported for PT. We conducted a GWAS and meta-analysis to identify genetic loci for aPTT and PT. The GWAS for aPTT was conducted in 9,240 individuals of European ancestry from the Atherosclerosis Risk in Communities (ARIC) study, and the GWAS for PT was conducted in 2,583 participants from the Genetic Study of Three Population Microisolates in South Tyrol (MICROS) and the Lothian Birth Cohorts (LBC) of 1921 and 1936. Replication was assessed in 1,041 to 3,467 individuals. For aPTT, previously reported associations with KNG1, HRG, F11, F12, and ABO were confirmed. A second independent association in ABO was identified and replicated (rs8176704, p = 4.26 10²⁴). Pooling the ARIC and replication data yielded two additional loci in F5 (rs6028, p = 3.22 10⁹) and AGBL1 (rs2469184, p = 3.61 10⁸). For PT, significant associations were identified and confirmed in F7 (rs561241, p = 3.71 10⁵⁶) and PROCR/EDEM2 (rs2295888, p = 5.25 10¹³). Assessment of existing gene expression and coronary artery disease (CAD) databases identified associations of five of the GWAS loci with altered gene expression and two with CAD. In summary, eight genetic loci that account for 29% of the variance in aPTT and two loci that account for 14% of the variance in PT were detected and supported by functional data.