Frequency of CYP2C9 polymorphisms affecting warfarin metabolism in a large anticoagulant clinic cohort.
Clin Biochem
; 39(6): 606-12, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16630605
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Polimorfismo Genético
/
Varfarina
/
Hidrocarboneto de Aril Hidroxilases
/
Anticoagulantes
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article