The p.V433M in cytochrome P450 4F2 (rs2108622, CYP4F2*3) is associated with higher warfarin dose requirements and a lower risk of hemorrhage among European Americans, but its role among African Americans is still unclear. In a prospective warfarin inception cohort study, Ms. Aditi Shendre, doctoral candidate in the department of epidemiology, mentored by Dr. Nita A. Limdi, professor in the department of neurology, at the University of Alabama at Birmingham, assessed “the influence of CYP4F2*3 on warfarin dose, anticoagulation control and risk of hemorrhage among European and African Americans.”
[Photo: Ms. Aditi Shendre]
The researchers used multivariable linear regression to calculate warfarin dose and PTTR, and survival analysis to evaluate time to therapeutic INR and stable dose, overanticoagulation, and bleeding among 1,238 patients taking warfarin. They discovered that “CYP4F2*3 was associated with higher dose among European Americans but not African Americans. Compared to the CYP4F2 wild-type genotype, *1/*3 was associated with a statistically nonsignificant increase in dose (4.5 percent, p=0.22) and *3/*3 was associated with a statistically significant increase in dose (13.2 percent, p=0.02). CYP4F2 genotype did not influence time to target INR, time to stable dose, or PTTR in either race group. CYP4F2*3/*3 was associated with a 31 percent lower risk of over anticoagulation (p=0.06). Incidence of hemorrhage was lower among participants with CYP4F2 *3/*3 compared to *1/*3 or *1/*1 (IRR=0.45; 95 percent CI: 0.14 – 1.11; p=0.09). After controlling for covariates, CYP4F2 *3/*3 was associated with a 52 percent lower risk of hemorrhage although this was not statistically significant (p=0.24).”
The study adds to the literature supporting the CYP4F2-warfarin dose association among European Americans but not African Americans. The CYP4F2-dose, CYP4F2-overanticoagulation, and CYP4F2-hemorrhage association observed follows a recessive pattern with possession of CYP4F2*3/*3 genotype likely demonstrating a protective effect. The team recommends further investigation to confirm results.
UAB co-investigators include Dr. Todd M. Brown, associate professor in the division of cardiovascular disease; and Dr. Nianjun Liu, associate professor, and Dr. T. Mark Beasley, professor, in the department of biostatistics.
“Race-Specific Influence of CYP4F2 on Dose and Risk of Hemorrhage among Warfarin Users” was published in February in the journal Pharmacotherapy.
Journal article: http://onlinelibrary.wiley.com/doi/10.1002/phar.1717/abstract