Body Simon C, Collard Charles D, Shernan Stanton K, Fox Amanda A, Liu Kuang-Yu, Ritchie Marylyn D, Perry Tjörvi E, Muehlschlegel Jochen D, Aranki Sary, Donahue Brian S, Pretorius Mias, Estrada Juan-Carlos, Ellinor Patrick T, Newton-Cheh Christopher, Seidman Christine E, Seidman J G, Herman Daniel S, Lichtner Peter, Meitinger Thomas, Pfeufer Arne, Kääb Stefan, Brown Nancy J, Roden Dan M, Darbar Dawood
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
Circ Cardiovasc Genet. 2009 Oct;2(5):499-506. doi: 10.1161/CIRCGENETICS.109.849075. Epub 2009 Aug 2.
Atrial fibrillation (AF) is the most common adverse event following coronary artery bypass graft 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 coronary artery bypass graft surgery.
Two prospectively collected cohorts of patients undergoing coronary artery bypass graft surgery, with or without concurrent valve surgery, at 3 US centers. From a discovery cohort of 959 patients, clinical and genomic multivariate predictors of postoperative AF were identified by genotyping 45 single-nucleotide polymorphisms (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 5 other linked SNPs independently predicted postoperative AF in the discovery cohort. Additive odds ratios for the 7 associated 4q25 SNPs ranged between 1.57 and 2.17 (P=8.0x10(-4) to 3.4x10(-6)). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort.
In 2 independently collected cardiac surgery cohorts, noncoding SNPs within the chromosome 4q25 region are independently associated with postoperative AF after coronary artery bypass graft surgery after adjusting for clinical covariates and multiple comparisons.
心房颤动（AF）是冠状动脉旁路移植术后最常见的不良事件。最近一项研究在非卧床人群中发现了与AF相关的4q25染色体变异。然而，它们在术后AF中的作用尚不清楚。我们假设4q25染色体区域的基因变异与冠状动脉旁路移植术后的AF独立相关。
在美国3个中心前瞻性收集了两组接受冠状动脉旁路移植手术的患者队列，其中一组同时进行瓣膜手术，另一组未进行。在一个由959名患者组成的发现队列中，通过对包含4q25位点的45个单核苷酸多态性（SNP）进行基因分型，确定了术后AF的临床和基因组多变量预测因子。然后在一个单独收集的494名患者的验证队列中评估了3个SNP。在对术后AF的临床预测因子进行调整并进行多次比较后，rs2200733、rs13143308以及其他5个连锁SNP在发现队列中独立预测了术后AF。7个相关的4q25 SNP的相加比值比在1.57至2.17之间（P = 8.0×10⁻⁴至3.4×10⁻⁶）。在验证队列中对rs2200733和rs13143308与术后AF的关联进行了测量和重复验证。
在2个独立收集的心脏手术队列中，在调整临床协变量和进行多次比较后，4q25染色体区域内的非编码SNP与冠状动脉旁路移植术后的AF独立相关。
