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Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment
- Source :
- Blood. 96:1816-1819
- Publication Year :
- 2000
- Publisher :
- American Society of Hematology, 2000.
-
Abstract
- Cytochrome P-450 2C9 is the principle enzyme that terminates the anticoagulant effect of warfarin. Genetic polymorphisms inCYP2C9 producing variants with altered catalytic properties have been identified. Patients (n = 561) with a target international normalized ratio (INR) of 2.5 who had been treated with warfarin for more than 2 months were anonymously genotyped for the wild-typeCYP2C9*1 allele and the 2C9*2 and2C9*3 variants. The mean maintenance dose of warfarin in patients who were wild-type for both alleles was 5.01 mg. The maintenance dose of warfarin was significantly related to genotype (Kruskall-Wallis, χ2 = 17.985, P = .001) with mean maintenance doses in patients with variant alleles between 61% and 86% of that in wild-type patients. The odds ratio for the2C9*2 allele in patients with a maintenance dose of 1.5 mg or less was 5.42 (95% CI 1.68-17.4). The odds ratio for one or more variant alleles in patients developing an INR of 8.0 or greater was 1.52 (95% CI 0.64-3.58). The SD of the mean INR, percentage of high INRs, and person-time spent in range were determined as parameters of stability. There was no difference between patients grouped according to genotype for any parameter of stability. This study confirmed an association between CYP2C9 genotype and warfarin sensitivity. However, the possession of a variant allele does not increase the likelihood of severe over-anticoagulation or stability of anticoagulation during long-term therapy.
- Subjects :
- medicine.medical_specialty
Time Factors
Genotype
medicine.drug_class
Statistics as Topic
Immunology
Biology
Biochemistry
Gastroenterology
Cohort Studies
Cytochrome P-450 Enzyme System
Risk Factors
Internal medicine
medicine
Humans
International Normalized Ratio
Blood Coagulation
CYP2C9
Alleles
Cytochrome P-450 CYP2C9
Polymorphism, Genetic
Dose-Response Relationship, Drug
Maintenance dose
Anticoagulant
Warfarin
Anticoagulants
Cell Biology
Hematology
Odds ratio
CYP2C9*3
Vitamin-K-epoxide reductase (warfarin-sensitive)
Endocrinology
Steroid 16-alpha-Hydroxylase
Steroid Hydroxylases
biology.protein
Aryl Hydrocarbon Hydroxylases
medicine.drug
Subjects
Details
- ISSN :
- 15280020 and 00064971
- Volume :
- 96
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....6e83868950a947b29be28a980dedbf50