title: Genetic variants associated with vein graft stenosis after coronary artery bypass grafting.
abstract: BACKGROUND
  Vein graft stenosis after coronary artery bypass grafting (CABG) is common. 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, who also underwent CABG and subsequent coronary angiography after CABG for clinical indications (n = 521). Cases were defined as individuals with ≥50% stenosis in any vein graft on any cardiac catheterization, and controls were defined as those who did not have vein graft stenosis on any subsequent cardiac catheterization. Multivariable logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) and vein graft stenosis.
  
  
  RESULTS
  Sixty-nine percent of patients had vein graft failure after CABG. Seven SNPs were significantly associated with vein graft stenosis, including intronic SNPs in the genes PALLD (Rs6854137, P = 3.77 × 10(-6)), ARID1B (Rs184074, P = 5.97 × 10(-6)), and TMEM123 (Rs11225247, P = 8.25 × 10(-6)); and intergenic SNPs near the genes ABCA13 (Rs10232860, P = 4.54 × 10(-6)), RMI2 (Rs9921338, P = 6.15 × 10(-6)), PRM2 (Rs7198849, P = 7.27 × 10(-6)), and TNFSF4 (Rs17346536, P = 9.33 × 10(-6)).
  
  
  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 merit further investigation, as they could assist in stratifying patients with multi-vessel coronary artery disease, which could lead to alterations in management and revascularization strategy.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Duke University Medical Center, Durham, NC. Email:asad.shah@duke.edu.
authors.forename: Asad A
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Carol
authors.initials: C
authors.lastname: Haynes
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Damian M
authors.initials: DM
authors.lastname: Craig
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sebek
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Grass
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Karen
authors.initials: K
authors.lastname: Abramson
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hauser
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.|Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Duke University Medical Center, Durham, NC. Email:asad.shah@duke.edu.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Smith
authors.affiliation: Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC.|Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
mesh_terms: D000368:Aged; D001026:Coronary Artery Bypass / Q000706:statistics & numerical data*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study; D006083:Graft Occlusion, Vascular / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009657:North Carolina / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D012501:Saphenous Vein / Q000637:transplantation*