by Amanda A. Fox, Mias Pretorius, Kuang-Yu Liu, Charles D. Collard, Tjorvi E. Perry, Stanton K. Shernan, Philip L. De Jager, David A. Hafler, Daniel S. Herman, Steven R. DePalma, Dan M. Roden, Jochen D. Muehlschlegel, Brian S. Donahue, Dawood Darbar, J. G. Seidman, Simon C. Body, Christine E. Seidman
Postoperative ventricular dysfunction (VnD) occurs in 9–20% of coronary artery bypass graft (CABG) surgical patients and is associated with increased postoperative morbidity and mortality. Understanding genetic causes of postoperative VnD should enhance patient risk stratification and improve treatment and prevention strategies. We aimed to determine if genetic variants associate with occurrence of in-hospital VnD after CABG surgery. Methods
A genome-wide association study identified single nucleotide polymorphisms (SNPs) associated with postoperative VnD in male subjects of European ancestry undergoing isolated primary CABG surgery with cardiopulmonary bypass. VnD was defined as the need for =2 inotropes or mechanical ventricular support after CABG surgery. Validated SNPs were assessed further in two replication CABG cohorts and meta-analysis was performed. Results
Over 100 SNPs were associated with VnD (P<10-4), with one SNP (rs17691914) encoded at 3p22.3 reaching genome-wide significance (Padditive model?=?2.14×10-8). Meta-analysis of validation and replication study data for 17 SNPs identified three SNPs associated with increased risk for developing postoperative VnD after adjusting for clinical risk factors. These SNPs are located at 3p22.3 (rs17691914, ORadditive model?=?2.01, P?=?0.0002), 3p14.2 (rs17061085, ORadditive model?=?1.70, P?=?0.0001) and 11q23.2 (rs12279572, ORrecessive model?=?2.19, P?=?0.001). Conclusions
No SNPs were consistently associated with strong risk (ORadditive model>2.1) of developing in-hospital VnD after CABG surgery. However, three genetic loci identified by meta-analysis were more modestly associated with development of postoperative VnD. Studies of larger cohorts to assess these loci as well as to define other genetic mechanisms and related biology that link genetic variants to postoperative ventricular dysfunction are warranted.