Related Experiment Video
Updated: May 5, 2026
RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells
Published on: February 13, 2013
Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in
Robert L Lobato1, William D White, Joseph P Mathew
1Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA.
Insights
Genetic variants in the thrombomodulin (THBD) gene are linked to higher long-term mortality after coronary artery bypass graft (CABG) surgery. These findings improve risk prediction models for cardiac surgery patients.
Area of Science:
- Cardiovascular Genetics
- Surgical Outcomes Research
- Molecular Epidemiology
Background:
- Long-term mortality after coronary artery bypass graft (CABG) surgery is a significant concern.
- Genetic factors influencing thrombotic and inflammatory pathways may impact patient outcomes.
- Identifying genetic predictors can enhance risk stratification for CABG patients.
Purpose of the Study:
- To investigate the association between genetic variations in thrombotic and inflammatory pathways and long-term mortality post-CABG.
- To identify specific genetic markers that independently predict mortality risk after cardiac surgery.
- To assess the utility of identified genetic variants in improving existing mortality prediction models.
Main Methods:
- Two independent cohorts of CABG patients were analyzed.
- A panel of 90 single-nucleotide polymorphisms (SNPs) in 49 candidate genes was screened.
- Cox proportional hazard models were used to identify predictors of all-cause mortality up to 5 years post-CABG.
Main Results:
- A common variant in the thrombomodulin (THBD) gene (rs1042579) was independently associated with increased mortality risk in the discovery cohort (HR, 2.26).
- This association was validated in an independent cohort using a linked SNP (rs3176123) (HR, 3.6).
- Both variants remained significant predictors after adjusting for clinical factors and multiple comparisons.
Conclusions:
- Common allelic variants in the THBD gene are independently associated with increased long-term mortality risk following CABG.
- These genetic markers significantly enhance the predictive ability of traditional postoperative mortality models.
- THBD gene variants represent potential targets for improved risk stratification in cardiac surgery.
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.
Related Concept Videos
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
01:29Pharmacogenomics: Identification of New Drug Targets
01:26Coronary Artery Disease II: Pathophysiology