Document Detail


Genetic variation of VKORC1 and CYP4F2 genes related to warfarin maintenance dose in patients with myocardial infarction.
MedLine Citation:
PMID:  21127708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The aim of this study was to investigate whether the VKORC1*3 (rs7294/9041 G > A), VKORC1*4 (rs17708472/6009 C > T), and CYP4F2 (rs2108622/1347 C > T) polymorphisms were associated with elevated warfarin maintenance dose requirements in patients with myocardial infarction (n = 105) from the Warfarin Aspirin Reinfarction Study (WARIS-II). We found significant associations between elevated warfarin dose requirements and VKORC1*3 and VKORC1*4 polymorphisms (P = .001 and P = .004, resp.), whereas CYP4F2 (1347 C > T) showed a weak association on higher warfarin dose requirements (P = .09). However, analysing these variant alleles in a regression analysis together with our previously reported data on VKORC1*2, CYP2C9*2 and CYP2C9*3 polymorphisms, gave no significant associations for neither VKORC1*3, VKORC1*4 nor CYP4F2 (1347 C > T). In conclusion, in patients with myocardial infarction, the individual contribution to warfarin dose requirements from VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms was negligible. Our results indicate that pharmacogenetic testing for VKORC1*2, CYP2C9*2 and CYP2C9*3 is more informative regarding warfarin dose requirements than testing for VKORC1*3, VKORC1*4, and CYP4F2 (1347 C > T) polymorphisms.
Authors:
Marianne K Kringen; Kari Bente Foss Haug; Runa M Grimholt; Camilla Stormo; Sigrid Narum; Mimi S Opdal; Jan Toralf Fosen; Armin P Piehler; Per W Johansen; Ingebjørg Seljeflot; Jens Petter Berg; Odd Brørs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-24
Journal Detail:
Title:  Journal of biomedicine & biotechnology     Volume:  2011     ISSN:  1110-7251     ISO Abbreviation:  J. Biomed. Biotechnol.     Publication Date:  2011  
Date Detail:
Created Date:  2010-12-03     Completed Date:  2011-03-29     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101135740     Medline TA:  J Biomed Biotechnol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  739751     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Oslo University Hospital, Ullevål, Oslo, Norway. m.k.kringen@medisin.uio.no
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MeSH Terms
Descriptor/Qualifier:
Cytochrome P-450 Enzyme System / genetics*
Dose-Response Relationship, Drug
Humans
Mixed Function Oxygenases / genetics*
Myocardial Infarction / drug therapy*,  genetics*
Polymorphism, Single Nucleotide
Regression Analysis
Statistics, Nonparametric
Warfarin / administration & dosage*
Chemical
Reg. No./Substance:
81-81-2/Warfarin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.-/Mixed Function Oxygenases; EC 1.14.13.30/CYP4F2 protein, human; EC 1.14.99.-/vitamin K epoxidase
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