Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.
Circulation
; 114(1 Suppl): I275-81, 2006 Jul 04.
Article
in En
| MEDLINE
| ID: mdl-16820586
ABSTRACT
BACKGROUND:
The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. METHODS ANDRESULTS:
We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703).CONCLUSIONS:
Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Postoperative Complications
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Cardiopulmonary Bypass
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Systemic Inflammatory Response Syndrome
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Polymorphism, Single Nucleotide
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Cardiac Surgical Procedures
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Myocardial Infarction
Type of study:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limits:
Aged
/
Female
/
Humans
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Male
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Middle aged
Language:
En
Journal:
Circulation
Year:
2006
Document type:
Article
Affiliation country: