Document Detail


Genetic variation, β-blockers, and perioperative myocardial infarction.
MedLine Citation:
PMID:  21918425     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Perioperative myocardial infarction is a common and potentially fatal complication after noncardiac surgery, particular among patients with cardiovascular risk factors. β-blockers have been considered a mainstay in prevention and treatment of perioperative myocardial infarction, yet recent evidence suggests that β-blockers may have an unfavorable risk profile in this setting, and the use has become controversial. What seems conspicuously absent from the current discussion is the appreciation of how much interindividual genetic variation influences the clinical response to β-blocker therapy. Genetic variation in the adrenergic signaling pathway is common, and has a major impact on adrenergic receptor function and β-blocker efficacy in other cardiovascular diseases, such as heart failure and hypertension. Genetic variation in the cytochrome P450 2D6, or CYP2D6, enzyme, which is responsible for the metabolism of most β-blockers, is also important and can lead to poor metabolizing of β-blockers (potential toxicity) or their ultra-rapid degradation (decreased efficacy). Here, we review the molecular, cellular, and physiologic consequences of polymorphisms in the adrenergic signaling pathway and CYP2D6 gene, and show that these are likely relevant factors influencing efficacy, safety, and toxicity of β-blocker therapy in prevention and treatment of perioperative myocardial infarction.
Authors:
Peter Nagele; Stephen B Liggett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Anesthesiology     Volume:  115     ISSN:  1528-1175     ISO Abbreviation:  Anesthesiology     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-29     Completed Date:  2012-01-18     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1316-27     Citation Subset:  AIM; IM    
Affiliation:
Division of Clinical and Translational Research, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. nagelep@wustl.edu
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / metabolism,  therapeutic use*
Cytochrome P-450 CYP2D6 / genetics*
Genetic Variation / genetics*
Humans
Myocardial Infarction / genetics,  prevention & control*
Perioperative Period
Polymorphism, Genetic / genetics
Postoperative Complications / genetics,  prevention & control*
Risk Factors
Grant Support
ID/Acronym/Agency:
1K23GM087534/GM/NIGMS NIH HHS; HL077101/HL/NHLBI NIH HHS; HL45967/HL/NHLBI NIH HHS; K23 GM087534/GM/NIGMS NIH HHS; K23 GM087534-01A1/GM/NIGMS NIH HHS; K23 GM087534-01A1S1/GM/NIGMS NIH HHS; UL1 RR024992/RR/NCRR NIH HHS; UL1RR024992/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; EC 1.14.14.1/Cytochrome P-450 CYP2D6
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