Document Detail


Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery.
MedLine Citation:
PMID:  19819472     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Approximately 10% of patients undergoing cardiac surgery have perioperative myocardial injury. A recent genome-wide association study identified an association between myocardial infarction in nonsurgical populations and common genetic variants on chromosome 9p21. We hypothesized that these variants are also associated with perioperative myocardial injury after isolated primary coronary artery bypass graft surgery.
METHODS: In a prospective observational study of 846 Caucasian patients undergoing primary coronary bypass surgery at 2 US centers, we genotyped 61 linkage-disequilibrium tagging single nucleotide polymorphisms, encompassing 436 kbp of the 9p21 region. A multivariable logistic model was used to adjust for previously identified clinical covariates of perioperative myocardial injury. Perioperative myocardial injury was defined as a postoperative day 1 cardiac troponin I in the top 10th percentile (>9.13 microg/L) of the cohort. Multiple testing of single nucleotide polymorphisms was corrected for with family-wise errors.
RESULTS: Prior myocardial infarction and longer cardiopulmonary bypass time were significant independent predictors of perioperative myocardial injury. Levels of postoperative cardiac troponin I were incrementally increased for each additional copy of the risk alleles of 3 single nucleotide polymorphisms: rs10116277, rs6475606, and rs2383207. Adjusted additive odds ratios ranged between 1.64 and 1.79 (asymptotic P value between 3.7 x 10(-3) and 6 x 10(-4)) and remained significantly associated with perioperative myocardial injury even after accounting for clinical covariates including severity of coronary disease, and multiple comparisons.
CONCLUSIONS: We have now demonstrated that common genetic variants in the same 9p21 locus, previously known to be associated with myocardial infarction in nonsurgical populations, are also associated with perioperative myocardial injury after coronary artery bypass grafting. Further investigation is warranted to elucidate functional mechanisms.
Authors:
Kuang-Yu Liu; Jochen D Muehlschlegel; Tjörvi E Perry; Amanda A Fox; Charles D Collard; Simon C Body; Stanton K Shernan
Publication Detail:
Type:  Journal Article; Multicenter Study     Date:  2009-10-12
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  139     ISSN:  1097-685X     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-28     Completed Date:  2010-03-02     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  483-8, 488.e1-2     Citation Subset:  AIM; IM    
Copyright Information:
2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
Affiliation:
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Chromosomes, Human, Pair 9 / genetics*
Coronary Artery Bypass / adverse effects*
Female
Genetic Variation*
Humans
Linkage Disequilibrium
Logistic Models
Male
Middle Aged
Myocardial Infarction / genetics*
Odds Ratio
Polymorphism, Single Nucleotide
Postoperative Complications / physiopathology
Prospective Studies
Troponin I / analysis
Grant Support
ID/Acronym/Agency:
K23 HL068774-01A1/HL/NHLBI NIH HHS; K23 HL068774-02/HL/NHLBI NIH HHS; K23 HL068774-03/HL/NHLBI NIH HHS; K23 HL068774-04/HL/NHLBI NIH HHS; K23 HL068774-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Troponin I
Comments/Corrections

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