Abstract 15841: Genome-Wide Association Identifies Genetic Variants Associated With Vein Graft Stenosis After Coronary Artery Bypass Grafting
Background: Vein graft stenosis after coronary artery bypass grafting (CABG) is common, with 50% of grafts occluded by 10 years. Identifying genes associated with vein graft stenosis after CABG could reveal novel mechanisms of disease and discriminate patients at risk for graft failure. We hypothesized that genome-wide association would identify these genes.
Methods: We performed a genome-wide association study on a subset of patients presenting for cardiac catheterization for concern of ischemic heart disease (CATHGEN biorepository) who also underwent CABG and subsequent coronary angiography at any time after CABG for clinical indications (N=517). Cases were defined as individuals with >50% stenosis in any vein graft on any cardiac catheterization (N=374), and controls were defined as those who did not have vein graft stenosis on any subsequent cardiac catheterization (N=143). Genotyping was done using the Illumina Human Omni1-Quad Bead Chip (908,165 single nucleotide polymorphisms [SNPs] which passed quality control measures). Multivariable logistic regression adjusted for race and sex was used to assess the association between SNPs which had minor allele frequencies (MAF) > 0.05 and vein graft stenosis.
Results: Fifty SNPs were significantly associated with vein graft stenosis (nominal P<1x10-4), representing SNPs in genes including (1) ACLS6, involved in formation of acyl-CoA from fatty acids, ATP, and CoA (rs440970, P=5x10-6); (2) SLIT3, a potent promoter of angiogenesis (rs12522564, P=8x10-6); (3) ODZ2, which encodes a membrane protein involved in transcriptional regulation (rs10214212, P=9x10-6); and (4) KCNJ16, which encodes a membrane potassium channel (rs11867479, P=1x10-5).
Conclusions: We have identified novel genetic variants that may predispose to risk of vein graft failure after CABG, many within biologically plausible pathways. These polymorphisms could assist in stratifying patients with multi-vessel coronary artery disease, which could lead to alterations in management and revascularization strategy.
- Coronary artery disease
- Genome-wide association studies (GWAS)
- Cardiac surgery
- Gene mutations
- Ischemic heart disease
- © 2011 by American Heart Association, Inc.