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Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses.

Publication ,  Journal Article
Lobato, RL; White, WD; Mathew, JP; Newman, MF; Smith, PK; McCants, CB; Alexander, JH; Podgoreanu, MV ...
Published in: Circulation
September 13, 2011

BACKGROUND: We tested the hypothesis that genetic variation in thrombotic and inflammatory pathways is independently associated with long-term mortality after coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: Two separate cohorts of patients undergoing CABG surgery at a single institution were examined, and all-cause mortality between 30 days and 5 years after the index CABG was ascertained from the National Death Index. In a discovery cohort of 1018 patients, a panel of 90 single-nucleotide polymorphisms (SNPs) in 49 candidate genes was tested with Cox proportional hazard models to identify clinical and genomic multivariate predictors of incident death. After adjustment for multiple comparisons and clinical predictors of mortality, the homozygote minor allele of a common variant in the thrombomodulin (THBD) gene (rs1042579) was independently associated with significantly increased risk of all-cause mortality (hazard ratio, 2.26; 95% CI, 1.31 to 3.92; P=0.003). Six tag SNPs in the THBD gene, 1 of which (rs3176123) in complete linkage disequilibrium with rs1042579, were then assessed in an independent validation cohort of 930 patients. After multivariate adjustment for the clinical predictors identified in the discovery cohort and multiple testing, the homozygote minor allele of rs3176123 independently predicted all-cause mortality (hazard ratio, 3.6; 95% CI, 1.67 to 7.78; P=0.001). CONCLUSIONS: In 2 independent cardiac surgery cohorts, linked common allelic variants in the THBD gene are independently associated with increased long-term mortality risk after CABG and significantly improve the classification ability of traditional postoperative mortality prediction models.

Duke Scholars

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

September 13, 2011

Volume

124

Issue

11 Suppl

Start / End Page

S143 / S148

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thrombomodulin
  • Survival Rate
  • Risk Factors
  • Prospective Studies
  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
 

Citation

APA
Chicago
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Lobato, R. L., White, W. D., Mathew, J. P., Newman, M. F., Smith, P. K., McCants, C. B., … Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team, . (2011). Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses. Circulation, 124(11 Suppl), S143–S148. https://doi.org/10.1161/CIRCULATIONAHA.110.008334
Lobato, Robert L., William D. White, Joseph P. Mathew, Mark F. Newman, Peter K. Smith, Charles B. McCants, John H. Alexander, Mihai V. Podgoreanu, and Mihai V. Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team. “Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses.Circulation 124, no. 11 Suppl (September 13, 2011): S143–48. https://doi.org/10.1161/CIRCULATIONAHA.110.008334.
Lobato RL, White WD, Mathew JP, Newman MF, Smith PK, McCants CB, et al. Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses. Circulation. 2011 Sep 13;124(11 Suppl):S143–8.
Lobato, Robert L., et al. “Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses.Circulation, vol. 124, no. 11 Suppl, Sept. 2011, pp. S143–48. Pubmed, doi:10.1161/CIRCULATIONAHA.110.008334.
Lobato RL, White WD, Mathew JP, Newman MF, Smith PK, McCants CB, Alexander JH, Podgoreanu MV, Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team. Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses. Circulation. 2011 Sep 13;124(11 Suppl):S143–S148.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

September 13, 2011

Volume

124

Issue

11 Suppl

Start / End Page

S143 / S148

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Thrombomodulin
  • Survival Rate
  • Risk Factors
  • Prospective Studies
  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans