Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK.
Curr Atheroscler Rep. 2011 Jun;13(3):193-201. doi: 10.1007/s11883-011-0178-z.
Recent genome-wide association studies have demonstrated that common genetic variants in a region of chromosome 9p21 confer risk of coronary artery disease (CAD) and other atherosclerotic conditions. Although the absolute increase in risk is small (some 20-30% increase in risk of CAD per copy of the deleterious alleles), the common occurrence of the variants means that their effect on the population risk of disease is estimated to be substantial. Studies investigating the relationship between risk variants and both "classical" and "emerging" atherosclerotic risk factors have found no evidence of association. This suggests that the effect of the 9p21 locus on atherosclerotic risk is mediated via a hitherto unknown pathway potentially amenable to therapeutic modulation. Investigation of potential disease mechanisms at this locus is therefore a focus of intense interest. In this review, we discuss the progress that has been made in the study of mechanisms and highlight the outstanding research questions.
最近的全基因组关联研究表明，9p21 染色体区域的常见遗传变异与冠状动脉疾病（CAD）和其他动脉粥样硬化疾病的风险相关。尽管风险增加的幅度很小（每增加一个有害等位基因，CAD 的风险就会增加 20-30%），但这些变异的常见发生意味着它们对疾病的人群风险的影响估计是相当大的。研究调查了风险变异与“经典”和“新兴”动脉粥样硬化风险因素之间的关系，没有发现关联的证据。这表明，9p21 基因座对动脉粥样硬化风险的影响是通过一种迄今为止未知的、可能适合治疗调节的途径介导的。因此，研究该基因座的潜在疾病机制是一个非常关注的焦点。在这篇综述中，我们讨论了在机制研究方面取得的进展，并强调了突出的研究问题。
