Document Detail


Frequency of CYP2C9 polymorphisms affecting warfarin metabolism in a large anticoagulant clinic cohort.
MedLine Citation:
PMID:  16630605     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To assess allele frequency and genotype distribution of CYP2C9 polymorphisms in patients (n = 189) attending an anticoagulant clinic in comparison to control patients (n = 177) and also to assess if the patients with variant genotypes require lower doses of warfarin. METHODS: Genotyping of the common CYP2C9 variants *2 and *3 was carried out by multiplexed PCR-RFLP while the *5 and *6 allele variants were genotyped by singleton PCR-RFLP. DNA sequencing was used to confirm genotype in all specimens with *3, *4 and *6 alleles. RESULTS: CYP2C9 allele frequencies in patients were 0.81 for *1, 0.11 for *2 and 0.08 for *3, compared to 0.88, 0.08 and 0.04, respectively, in controls. Patients with *1/*3 and *X/*X (where *X is *2 or *3) genotypes required 32 to 67% less warfarin in comparison to patients with the normal *1/*1 genotype. Other alleles were observed in less than 1% of subjects. CONCLUSIONS: Allele frequencies and genotypes for CYP2C9*2 and *3 variants in patients on warfarin are not statistically different from controls whether or not they are stratified for ethnicity. Less common genotypes (*4, *5, *6) do not contribute significantly to warfarin sensitivity among patients attending a routine anticoagulation clinic. CYP2C9 genotype predicts warfarin dosage even in an uncontrolled, retrospective survey of unselected patients on warfarin therapy.
Authors:
Majid Moridani; Lei Fu; Rita Selby; Francisco Yun; Tatjana Sukovic; Betty Wong; David E C Cole
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-04-21
Journal Detail:
Title:  Clinical biochemistry     Volume:  39     ISSN:  0009-9120     ISO Abbreviation:  Clin. Biochem.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-23     Completed Date:  2006-08-30     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0133660     Medline TA:  Clin Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  606-12     Citation Subset:  IM    
Affiliation:
School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
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MeSH Terms
Descriptor/Qualifier:
Aged
Anticoagulants / pharmacokinetics*
Aryl Hydrocarbon Hydroxylases / genetics*
Base Sequence
Cohort Studies
DNA Primers
Female
Genotype
Humans
International Normalized Ratio
Male
Middle Aged
Polymerase Chain Reaction
Polymorphism, Genetic*
Retrospective Studies
Thrombosis / prevention & control
Warfarin / pharmacokinetics*
Chemical
Reg. No./Substance:
0/Anticoagulants; 0/DNA Primers; 81-81-2/Warfarin; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/CYP2C9 protein, human

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