Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses.
Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses.
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DOI：
10.1161/circulationaha.110.008334
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发表时间：
2011-09-13
期刊：
影响因子：
37.8
通讯作者：
Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative Team
中科院分区：
文献类型：
--
作者：
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
We tested the hypothesis that genetic variation in thrombotic and inflammatory pathways is independently associated with long-term mortality following coronary artery bypass grafting (CABG). Two separate cohorts of patients undergoing CABG 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 in 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 (HR 2.26; 95%CI, 1.31–3.92; p=0.003). Six tag SNPs in the THBD gene, one of which (rs3176123) in complete linkage disequilibrium with rs1042579, were then assessed in an independent validation cohort of 930 patients. Following 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 (HR 3.6; 95%CI, 1.67–7.78; p=0.001). In two independent cardiac surgery cohorts, linked common allelic variants in the THBD gene are independently associated with increased long-term mortality risk following CABG, and significantly improve the classification ability of traditional postoperative mortality prediction models.
