Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery

Kuang Yu Liu, Jochen D. Muehlschlegel, Tjörvi E. Perry, Amanda A. Fox, Charles D. Collard, Simon C. Body, Stanton K. Shernan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 μg/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 × 10-3 and 6 × 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.

Original languageEnglish (US)
JournalJournal of Thoracic and Cardiovascular Surgery
Volume139
Issue number2
DOIs
StatePublished - Feb 2010

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Coronary Artery Bypass
Chromosomes
Transplants
Wounds and Injuries
Single Nucleotide Polymorphism
Troponin I
Myocardial Infarction
Genome-Wide Association Study
Linkage Disequilibrium
Population Genetics
Cardiopulmonary Bypass
Thoracic Surgery
Observational Studies
Coronary Disease
Logistic Models
Alleles
Odds Ratio
Prospective Studies
Population

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Pulmonary and Respiratory Medicine

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Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery. / Liu, Kuang Yu; Muehlschlegel, Jochen D.; Perry, Tjörvi E.; Fox, Amanda A.; Collard, Charles D.; Body, Simon C.; Shernan, Stanton K.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 139, No. 2, 02.2010.

Research output: Contribution to journalArticle

Liu, Kuang Yu ; Muehlschlegel, Jochen D. ; Perry, Tjörvi E. ; Fox, Amanda A. ; Collard, Charles D. ; Body, Simon C. ; Shernan, Stanton K. / Common genetic variants on chromosome 9p21 predict perioperative myocardial injury after coronary artery bypass graft surgery. In: Journal of Thoracic and Cardiovascular Surgery. 2010 ; Vol. 139, No. 2.
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abstract = "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 μg/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 × 10-3 and 6 × 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.",
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AU - Body, Simon C.

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AB - 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 μg/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 × 10-3 and 6 × 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.

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