Warfarin Dosing in Patients With CYP2C95 Variant Alleles

• Published in: Clinical pharmacology and therapeutics 2022-04, Vol.111 (4), p.950-955
• Main Authors: Lindley, Kathryn J., Limdi, Nita A., Cavallari, Larisa H., Perera, Minoli A., Lenzini, Petra, Johnson, Julie A., Wu, Alan H. B., Ridker, Paul M, King, Cristi R., Eby, Charles S., Patel, Shitalben, Shah, Shimoli V., Beasley, T. Mark, Li, Juan, Gage, Brian F.
• Format: Article
• Language: English
• Subjects: Alleles; Anticoagulants - adverse effects; Aryl Hydrocarbon Hydroxylases - genetics; Cytochrome P-450 CYP2C9 - genetics; Dose-Response Relationship, Drug; Female; Genotype; Humans; Male; Polymorphism, Single Nucleotide; Vitamin K Epoxide Reductases - genetics; Warfarin - adverse effects
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1002/cpt.2549

Pharmacogenetic dosing improves the accuracy of warfarin dosing, but current pharmacogenetic dosing algorithms are less accurate in populations of African ancestry. The cytochrome P450 2C9*5 (CYP2C9*5) allele is found almost exclusively in populations of African ancestry, and in vitro studies suggest CYP2C9*5 is associated with reduced clearance of warfarin. The clinical relevance of this single‐nucleotide variation (SNV) (formerly SNP) is uncertain. In this multicentered study of 2,298 patients (49% female, 35% Black) taking warfarin, we quantified the association between the CYP2C9*5 allele and warfarin requirements. The CYP2C9*5 SNV was present in 2.3% of Black and 0.07% of White patients. Without taking CYP2C9*5 into account, pharmacogenetic algorithms that include other SNVs overestimated the warfarin dose by 30% (95% confidence interval (19–40%), P