Thrombomodulin Gene Variants Up Post-CABG Mortality Risk

Homozygote minor allele of rs3176123 independently predicts all-cause mortality

FRIDAY, Sept. 16 (HealthDay News) -- Genetic variants in the thrombomodulin gene (THBD) are independently associated with an increased risk of long-term all-cause mortality after coronary artery bypass graft (CABG) surgery, according to a study published in the Sept. 13 issue of Circulation.

Robert L. Lobato, M.D., from the Stanford University School of Medicine in California, and colleagues investigated the association of genetic variants in thrombotic and inflammatory pathways with long-term mortality in patients from two study cohorts who underwent CABG surgery. The National Death Index was used to identify all-cause mortality between 30 days and five years after surgery. Clinical and genomic multivariate predictors of incident death were identified by testing a panel of 90 single-nucleotide polymorphisms (SNPs) in 49 candidate genes in a discovery cohort of 1,018 patients. In a validation cohort of 930 patients, six tag SNPs in the thrombomodulin THBD gene were assessed, one of which (rs3176123) was in complete linkage disequilibrium with rs1042579.

The investigators found that the homozygote minor allele of a common variant in the THBD gene (rs1042579) was independently correlated with a significantly elevated risk of all-cause mortality (hazard ratio [HR], 2.26), after adjusting for multiple comparisons and clinical predictors of mortality. The homozygote minor allele of rs3176123 significantly and independently predicted all-cause mortality (HR, 3.6), after adjustment for the clinical predictors identified in the discovery cohort and multiple testing.

"In two independent cardiac surgery cohorts, linked common allelic variants in the THBD gene are independently associated with increased long-term mortality risk after CABG," the authors write.

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