Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery.
Variation in the 4q25 chromosomal locus predicts atrial fibrillation after coronary artery bypass graft surgery.
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DOI：
10.1161/circgenetics.109.849075
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发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
Darbar D
中科院分区：
文献类型：
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作者：
Body SC;Collard CD;Shernan SK;Fox AA;Liu KY;Ritchie MD;Perry TE;Muehlschlegel JD;Aranki S;Donahue BS;Pretorius M;Estrada JC;Ellinor PT;Newton-Cheh C;Seidman CE;Seidman JG;Herman DS;Lichtner P;Meitinger T;Pfeufer A;Kääb S;Brown NJ;Roden DM;Darbar D
房颤（AF）是冠状动脉搭桥术（CABG）术后最常见的不良事件。最近的一项研究在流动人群中发现了与房颤相关的染色体4q25变异。然而，它们在术后房颤中的作用尚不清楚。我们假设4q25染色体区域的遗传变异与CABG术后房颤独立相关。两组前瞻性收集的患者在美国三个中心接受CABG手术，有或没有并发瓣膜。从959例患者的发现队列中，通过对包含4q25位点的45个snp进行基因分型，确定了术后房颤的临床和基因组多变量预测因子。然后在单独收集的494例患者的验证队列中评估三个snp。在对术后房颤的临床预测因素进行调整和多次比较后，在发现队列中，rs2200733、rs13143308和其他5个连锁snp独立预测了术后房颤。7个相关4q25 snp的加性or值在1.57 ~ 2.17之间（P值为8.0 × 10-4 ~ 3.4 × 10-6）。在验证队列中测量并重复rs2200733和rs13143308与术后房颤的关联。在两个独立收集的心脏手术队列中，在调整临床协变量和多重比较后，染色体4q25区域内的非编码snp与CABG术后房颤独立相关。
Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft (CABG) surgery. A recent study identified chromosome 4q25 variants associated with AF in ambulatory populations. However, their role in postoperative AF is unknown. We hypothesized that genetic variants in the 4q25 chromosomal region are independently associated with postoperative AF after CABG surgery. Two prospectively collected cohorts of patients undergoing CABG, with or without concurrent valve, surgery at three U.S. centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 SNPs encompassing the 4q25 locus. Three SNPs were then assessed in a separately-collected validation cohort of 494 patients. After adjustment for clinical predictors of postoperative AF, and multiple comparisons, rs2200733, rs13143308 and five other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive ORs for the seven associated 4q25 SNPs ranged between 1.57 and 2.17 (P value 8.0 × 10-4 − 3.4 × 10-6). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. In two independently collected cardiac surgery cohorts, non-coding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after CABG surgery after adjusting for clinical covariates and multiple comparisons.