Wei Tiemin, Song Jingjing, Xu Min, Lv Lingchun, Liu Chong, Shen Jiayi, Huang Ying
Vasculocardiology Department, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, Zhejiang, P.R. China.
Department of Radiology, The Fifth Affiliated Hospital of Wenzhou Medical University, Affiliated Lishui Hospital of Zhejiang University, The Central Hospital of Zhejiang Lishui, Lishui, Zhejiang, P.R. China.
Oncotarget. 2016 Jul 5;7(27):42617-42624. doi: 10.18632/oncotarget.9422.
Postoperative atrial fibrillation (POAF) is a serious, common complication after coronary artery bypass grafting (CABG) surgery. Recently, 5 novel loci were identified to be associated with atrial fibrillation susceptibility using a combination of genotyping, eQTL mapping, and functional validation. In current study, we aim to evaluated the positive findings for POAF susceptibility after CABG among Chinese population, using a population-based, two-stage, nested case-control study with 1,400 patients. NEURL rs12415501 and CAND2 rs4642101 were significantly associated with POAF susceptibility after CABG among Chinese population in both stages. When pooled together, the ORs for each additional copy of minor allele was 1.29 (95% CI: 1.13-1.48, P = 1.7×10-4) for NEURL rs12415501, and 1.21 (95% CI: 1.08-1.36, P = 9.8×10-4) for CAND2 rs4642101. Functional validation experiments found the AF risk allele of NEURL rs6584555 and CAND2 rs4642101 correlated with an increased expression of its corresponding genes (P<0.001). In this independently collected cardiac surgery cohort, we replicated the previous findings, and 2 novel loci are independently associated with POAF risk in patients who undergo CABG surgery in Chinese population.
术后房颤(POAF)是冠状动脉旁路移植术(CABG)后一种严重且常见的并发症。最近,通过基因分型、表达数量性状位点(eQTL)定位和功能验证相结合的方法,确定了5个与房颤易感性相关的新基因座。在本研究中,我们旨在通过一项基于人群的两阶段巢式病例对照研究,对1400例患者进行评估,以验证中国人群CABG术后POAF易感性的阳性研究结果。在两个阶段中,NEURL基因的rs12415501位点和CAND2基因的rs4642101位点均与中国人群CABG术后的POAF易感性显著相关。合并分析时,NEURL基因rs12415501位点每增加一个次要等位基因拷贝,其比值比(OR)为1.29(95%置信区间:1.13 - 1.48,P = 1.7×10⁻⁴);CAND2基因rs4642101位点每增加一个次要等位基因拷贝,其OR为1.21(95%置信区间:1.08 - 1.36,P = 9.8×10⁻⁴)。功能验证实验发现,NEURL基因rs6584555位点和CAND2基因rs4642101位点的房颤风险等位基因与其相应基因表达增加相关(P < 0.001)。在这个独立收集的心脏手术队列中,我们重复了之前的研究结果,并且在中国人群中,发现了2个新的基因座与接受CABG手术患者的POAF风险独立相关。