Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction.
Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction.
复制标题
全基因组关联研究确定了急性心肌梗死中21q21的易感性基因座。
作者：
在急性心肌梗死期间，室颤导致的心源性猝死是导致总死亡和心血管死亡的主要原因。据我们所知，我们在这里报告了第一个关于这一特征的全基因组关联研究，来自荷兰心律失常遗传学(Agnes)的研究，对972名首次急性心肌梗死患者进行了研究，其中515人有室颤，457人没有。与室颤的关联最显著的是21q21(rs2824292，优势比=1.78，95%可信区间1.47~2.13，P=3.3×10−10)。Rs2824292与室颤的关联在一个独立的病例对照组中被重复(优势比=1.49，95%可信区间1.14~1.95，P=0.004)，该病例对照组包括14 6例院外心脏骤停合并室颤患者和391例心肌梗塞存活患者(对照组)。与这种SNP最接近的基因是CXADR，它编码一种病毒受体，以前与心肌炎和扩张型心肌病有关，最近被发现是心脏传导的调节器。该基因座此前未被认为与心律失常易感性有关。
Sudden cardiac death from ventricular fibrillation during acute myocardial infarction is a leading cause of total and cardiovascular mortality. To our knowledge, we here report the first genome-wide association study for this trait, conducted in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillation was found at 21q21 (rs2824292, odds ratio = 1.78, 95% CI 1.47–2.13, P = 3.3 × 10−10). The association of rs2824292 with ventricular fibrillation was replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest individuals with myocardial infarction complicated by ventricular fibrillation and 391 individuals who survived a myocardial infarction (controls) (odds ratio = 1.49, 95% CI 1.14–1.95, P = 0.004). The closest gene to this SNP is CXADR, which encodes a viral receptor previously implicated in myocarditis and dilated cardiomyopathy and which has recently been identified as a modulator of cardiac conduction. This locus has not previously been implicated in arrhythmia susceptibility.
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影响因子：
15.3
作者：
Lisewski, Ulrike;Shi, Yu;Wrackmeyer, Uta;Fischer, Robert;Chen, Chen;Schirdewan, Alexander;Juettner, Rene;Rathjen, Fritz;Poller, Wolfgang;Radke, Michael H.;Gotthardt, Michael
通讯作者：
Gotthardt, Michael
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
30.8
作者：
Arking, Dan E.;Pfeufer, Arne;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
影响因子：
30.8
作者：
Pfeufer, Arne;Sanna, Serena;Arking, Dan E.;Mueller, Martina;Gateva, Vesela;Fuchsberger, Christian;Ehret, Georg B.;Orru, Marco;Pattaro, Cristian;Koettgen, Anna;Perz, Siegfried;Usala, Gianluca;Barbalic, Maja;Li, Man;Puetz, Benno;Scuteri, Angelo;Prineas, Ronald J.;Sinner, Moritz F.;Gieger, Christian;Najjar, Samer S.;Kao, W. H. Linda;Muehleisen, Thomas W.;Dei, Mariano;Happle, Christine;Moehlenkamp, Stefan;Crisponi, Laura;Erbel, Raimund;Joeckel, Karl-Heinz;Naitza, Silvia;Steinbeck, Gerhard;Marroni, Fabio;Hicks, Andrew A.;Lakatta, Edward;Mueller-Myhsok, Bertram;Pramstaller, Peter P.;Wichmann, H-Erich;Schlessinger, David;Boerwinkle, Eric;Meitinger, Thomas;Uda, Manuela;Coresh, Josef;Kaeaeb, Stefan;Abecasis, Goncalo R.;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda
影响因子：
3.5
作者：
Eijgelsheim, Mark;Newton-Cheh, Christopher;Stricker, Bruno H. C.
通讯作者：
Stricker, Bruno H. C.