ArticleEuropean journal of clinical pharmacology2015
CYP2C19*17 affects R-warfarin plasma clearance and warfarin INR/dose ratio in patients on stable warfarin maintenance therapy.
Article in European journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Association between gene polymorphisms and initial warfarin therapy in patients after heart valve surgery.Pharmacological reports : PR · 2024Article
- The pharmacoepigenomics informatics pipeline defines a pathway of novel and known warfarin pharmacogenomics variants.Pharmacogenomics · 2018Article
- Quantitative Assessment of CYP2C9 Genetic Polymorphisms Effect on the Oral Clearance of S-Warfarin in Healthy Subjects.Molecular diagnosis & therapy · 2017Article
- Linkage disequilibrium between the CYP2C19*2,*17 and CYP2C9*1 alleles and impact of VKORC1, CYP2C9, CYP2C19 gene polymorphisms and gene-gene interactions on warfarin therapy.Journal of thrombosis and thrombolysis · 2017Article
- Interethnic variation of CYP2C19 alleles, 'predicted' phenotypes and 'measured' metabolic phenotypes across world populations.The pharmacogenomics journal · 2016Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeWe aimed to assess the influence of CYP2C19*17 on R-warfarin clearance as well as the effect of CYP2C19, CYP2C8, CYP2C9, and VKORC1 polymorphisms together with non-genetic factors on warfarin international normalized ratio (INR)/daily dose.
methodsOne hundred fifty Caucasian Italian outpatients with data on steady-state plasma concentrations of S- and R-warfarin were genotyped for CYP2C19 (*2, *3, *4, *17), CYP2C9 (*2, *3), CYP2C8*3, and VKORC1*2. The statistical analysis was performed on the effect of genotypes/haplotypes, age, sex, and body weight on the clearance of warfarin enantiomers and dose-normalized INR.
resultsR-warfarin clearance was 32% higher in carriers of CYP2C19*17 than in carriers of CYP2C19*2 (mean 2.5 mL/min, 95% confidence interval (CI) 2.3-2.8 vs. 1.9 mL/min, 95% CI 1.7-2.2; P post hoc = 0.01). Patients with CYP2C19*1/*1 genotype had an intermediate clearance (mean 2.1 mL/min, 95% CI 1.8-2.4). The genotypes of VKORC1, CYP2C9, and CYP2C19, together with non-genetic factors (age, sex, and body weight) explained 52% of the variability in warfarin INR/daily dose, of which CYP2C19 genotypes accounted for 7%.
conclusionsThis is the first study to include the gain-of-function CYP2C19*17 allele when assessing the impact of CYP2C19 polymorphisms on the clearance of warfarin enantiomers. CYP2C19 genotypes influenced the clearance of R-warfarin and contributed significantly to the variability in INR/daily dose, indirectly indicating a clinical relevance of R-warfarin.
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