Zeller Tanja, Seiffert Moritz, Müller Christian, Scholz Markus, Schäffer Anna, Ojeda Francisco, Drexel Heinz, Mündlein Axel, Kleber Marcus E, März Winfried, Sinning Christoph, Brunner Fabian J, Waldeyer Christoph, Keller Till, Saely Christoph H, Sydow Karsten, Thiery Joachim, Teupser Daniel, Blankenberg Stefan, Schnabel Renate
Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany.
DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
Front Cardiovasc Med. 2017 Sep 20;4:57. doi: 10.3389/fcvm.2017.00057. eCollection 2017.
Coronary artery disease (CAD) has a complex etiology involving numerous environmental and genetic factors of disease risk. To date, the genetic 9p21 locus represents the most robust genetic finding for prevalent and incident CAD. However, limited information is available on the genetic background of the severity and distribution of CAD. CAD manifests itself as stable CAD or acute coronary syndrome. The Gensini score quantifies the extent CAD but requires coronary angiography. Here, we aimed to identify novel genetic variants associated with Gensini score severity and distribution of CAD. A two-stage approach including a discovery and a replication stage was used to assess genetic variants. In the discovery phase, a meta-analysis of genome-wide association data of 4,930 CAD-subjects assessed by the Gensini score was performed. Selected single nucleotide polymorphisms (SNPs) were replicated in 2,283 CAD-subjects by genotyping. We identified genetic loci located on chromosome 2 and 9 to be associated with Gensini score severity and distribution of CAD in the discovery stage. Although the loci on chromosome 2 could not be replicated in the second stage, the known CAD-locus on chromosome 9p21, represented by rs133349, was identified and, thus, was confirmed as risk locus for CAD severity.
冠状动脉疾病（CAD）病因复杂，涉及众多疾病风险的环境和遗传因素。迄今为止，9p21基因座是已发现的与CAD患病率和发病率关联最为紧密的基因。然而，关于CAD严重程度和分布的遗传背景信息有限。CAD表现为稳定型CAD或急性冠状动脉综合征。Gensini评分可量化CAD的程度，但需要进行冠状动脉造影。在此，我们旨在识别与CAD的Gensini评分严重程度和分布相关的新基因变异。采用包括发现阶段和复制阶段的两阶段方法来评估基因变异。在发现阶段，对4930名通过Gensini评分评估的CAD受试者的全基因组关联数据进行了荟萃分析。通过基因分型在2283名CAD受试者中对选定的单核苷酸多态性（SNP）进行了复制。我们在发现阶段确定位于2号和9号染色体上的基因座与CAD的Gensini评分严重程度和分布相关。尽管2号染色体上的基因座在第二阶段未能得到复制，但由rs133349代表的9p21染色体上已知的CAD基因座被识别出来，因此被确认为CAD严重程度的风险基因座。
