Researchers have identified a genetic variant in black patients that may explain their variable response to the blood thinner warfarin and has the potential to improve dosing algorithms, results from the first genome-wide association study on the topic indicate.
Reducing the average 40 mg average weekly warfarin dose by 6.92 mg could help black patients with one copy of the rs12777823 genetic variant obtain the medication’s full benefits, Julie Johnson, PharmD, of the Center for Pharmacogenics at the University of Florida in Gainesville, and colleagues reported in Lancet.
For patients with two copies of this single-nucleotide polymorphism (SNP) in the CYP2C cluster on chromosome 10, a 9 mg/per week reduction would achieve appropriate dosing.
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Including rs12777823 as a genetic marker in International Warfarin Pharmacogenetics Consortium (IWPC) dosing algorithms resulted in a 21% relative improvement, the researchers found.
Although warfarin is widely prescribed as an anticoagulant for patients with atrial fibrillation, a history of previous blood clots of after major surgery, dosing requirements vary from patient to patient. Difficulty determining the optimal dose is common, and the medication is responsible for one-third of adverse drug reaction hospitalizations in U.S. patients aged older than 65 years.
Researchers know that SNP genes encoding CYP2C9 and VKORC1 affect the way warfarin is metabolized, accounting for about 30% of warfarin variability in patients of European and Asian descent, but just 7% and 10% of those of African descent.
As previous genome-wide association studies have not included African Americans, Johnson and colleagues collected and analyzed DNA samples from 533 African-American adults taking stable doses of warfarin from the IWPC and the University of Alabama Birmingham School of Medicine.
After finding a strong association between rs12777823 and warfarin dose requirements, they confirmed the findings in an additional cohort of 432 participants.
“A novel CYP2C single nucleotide polymorphism exerts a clinically relevant effect on warfarin dose in African Americans, independent of CYP2C9*2 and CYP2C9*3,” the researchers wrote. “Incorporation of this variant into pharmacogenetic dosing algorithms could improve warfarin dose prediction in this population.”
However, they warned the findings did not prove causation and called for additional studies to confirm the findings.
