| Thrombomodulin gene variants are associated with increased mortality after coronary artery bypass surgery in replicated analyses. | |
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MedLine Citation:
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PMID: 21911804 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Robert L Lobato; William D White; Joseph P Mathew; Mark F Newman; Peter K Smith; Charles B McCants; John H Alexander; Mihai V Podgoreanu; |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation Volume: 124 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2011 Sep |
Date Detail:
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Created Date: 2011-09-13 Completed Date: 2011-11-03 Revised Date: 2012-10-09 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: S143-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aged Cohort Studies Coronary Artery Bypass* Coronary Artery Disease / mortality*, surgery* Female Genetic Predisposition to Disease Genotype Humans Male Middle Aged Polymorphism, Single Nucleotide / genetics* Proportional Hazards Models Prospective Studies Risk Factors Survival Rate Thrombomodulin / genetics* Treatment Outcome |
| Grant Support | |
ID/Acronym/Agency:
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R01 HL075273-05/HL/NHLBI NIH HHS; R01 HL092071-04/HL/NHLBI NIH HHS; R01-AG09663/AG/NIA NIH HHS; R01-HL075273/HL/NHLBI NIH HHS; R01-HL092071/HL/NHLBI NIH HHS; R01-HL54316/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Thrombomodulin |
| Investigator | |
Investigator/Affiliation:
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Andrew Allen / ; Carmelo Milano / ; Eugene Moretti / ; Joseph P Mathew / ; Madhav Swaminathan / ; Mark Stafford-Smith / ; Ian J Welsby / ; G Burkhard Mackensen / ; Mark F Newman / ; R Duane Davis / ; Bonita Funk / ; Barbara Phillips-Bute / ; Donald Glower / ; Katherine P Grichnik / ; Roger L Hall / ; Michael P Smith / ; Elizabeth Hauser / ; Peter K Smith / ; Steven E Hill / ; Robert Jones / ; Daniel Laskowitz / ; Andrew Lodge / ; William D White / ; Willem Lombard / ; Huntington F Willard / ; Geoffrey S Ginsburg / ; Miklos D Kertai / ; David B Goldstein / ; Jeffrey Gaca / ; Mihai V Podgoreanu / |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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