Variation in the 4q25 Chromosomal Locus Predicts Atrial Fibrillation After Coronary Artery Bypass Graft Surgery

被引：88

作者：

Body, Simon C. ^{[1
]}

Collard, Charles D. ^{[4
]}

Shernan, Stanton K. ^{[1
]}

Fox, Amanda A. ^{[1
]}

Liu, Kuang-Yu ^{[1
]}

Ritchie, Marylyn D. ^{[8
]}

Perry, Tjoervi E. ^{[1
]}

Muehlschlegel, Jochen D. ^{[1
]}

Aranki, Sary ^{[2
]}

Donahue, Brian S. ^{[5
]}

Pretorius, Mias ^{[5
]}

Estrada, Juan-Carlos ^{[6
]}

Ellinor, Patrick T. ^{[11
]}

Newton-Cheh, Christopher ^{[11
,12
,13
]}

Seidman, Christine E. ^{[3
,9
]}

Seidman, J. G. ^{[9
,10
]}

Herman, Daniel S. ^{[9
]}

Lichtner, Peter ^{[14
]}

Meitinger, Thomas ^{[14
]}

Pfeufer, Arne ^{[14
]}

Kaeaeb, Stefan ^{[14
,15
]}

Brown, Nancy J. ^{[6
,7
]}

Roden, Dan M. ^{[6
,7
]}

Darbar, Dawood ^{[6
]}

机构：

[1] Harvard Univ, Dept Anesthesiol Perioperat & Pain Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA

[2] Harvard Univ, Div Cardiac Surg, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA

[3] Harvard Univ, Howard Hughes Med Inst, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA

[4] St Lukes Episcopal Hosp, Texas Heart Inst, Baylor Coll Med, Div Cardiovasc Anesthesia, Houston, TX USA

[5] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37212 USA

[6] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA

[7] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA

[8] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA

[9] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Partners HealthCare Ctr Genet & Genom, Boston, MA 02115 USA

[11] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA

[12] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[13] Broad Inst Harvard & MIT, Program Med & Populat Genet, Boston, MA USA

[14] Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany

[15] Klinikum Univ Munchen Grosshadern, Med Klin, Munich, Germany

来源：

CIRCULATION-CARDIOVASCULAR GENETICS | 2009年 / 2卷 / 05期

关键词：

atrial fibrillation; arrhythmia; postoperative complication; heart surgery; genetics; GENE-MUTATIONS; RISK-FACTOR; POLYMORPHISM; IDENTITY; SCN5A; SNPS;

D O I：

10.1161/CIRCGENETICS.109.849075

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-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. Methods and Results-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 = 8.0 X 10(-4) to 3.4 X 10(-6)). Association with postoperative AF were measured and replicated for rs2200733 and rs13143308 in the validation cohort. Conclusions-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. (Circ Cardiovasc Genet. 2009;2:499-506.)

引用

页码：499 / U197

页数：10

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