Abstract 21392: Genome-wide Association Study of Vein Graft Disease Following Coronary Artery Bypass Surgery
Background: Despite frequent use of internal thoracic artery grafts, autologous saphenous vein remains the most commonly used conduit for coronary artery bypass grafting (CABG), but its long-term benefits are limited by the development of vein graft failure. We conducted a genome-wide association study to identify potential genetic susceptibility to aortocoronary vein graft disease.
Methods: A cohort of N=1065 patients who underwent primary CABG and completed follow-up quantitative angiography as part of the PREVENT-IV trial were genotyped using the Illumina 610quad chip. The primary endpoint was per patient incidence of angiographic vein graft disease (≥50% stenosis in at least one vein graft).
Results: The primary endpoint occurred in 543 patients (51%). Following adjustment for population stratification, we identified 3 common single nucleotide polymorphisms associated with incidence of vein graft disease in additive genetic models (p<10-6, FDR=0.23). The top hit involves an intronic variant in the PID1 gene (phosphotyrosine interaction domain containing 1), an important regulator of LDL receptor biology and cell proliferation.
Conclusions: The thromboproliferative process underlying progression of coronary bypass vein graft disease appears to be genetically determined. Follow-up analyses including replication in an independent cohort, per graft analyses and using continuous quantitative angiographic endpoints (mean vein graft lumen diameter) are ongoing.
- © 2010 by American Heart Association, Inc.