Dose Impacts African Americans

Genetic Variations Impact Warfarin Doses For African Americans

A common genetic variation that can impact the therapeutic dose of the blood-thinning drug warfarin among African Americans has been found, according to a new report in The Lancet.

The finding revealed that people of African ancestry who have the rs12777823 variant require a notably lower dose of warfarin to achieve all the advantages, compared to those without this single-nucleotide polymorphism (SNP).

Julie Johnson from the University of Florida and lead researcher explained:

"Adding this genetic marker - found in more than 40% of African American patients in the study - to standard dosing algorithms improved the predictability of warfarin dosing by 21% in these individuals, which has the potential to increase the safety and effectiveness of this notoriously hard to dose drug."

Warfarin is used to prevent blood clots in patients who experienceatrial fibrillation, have a history of blood clots, or after major surgery. It is one of the most prescribed drugs around the world, adding up to around 35 million prescriptions in the USA in 2011.

Dosage requirements range widely between people, making it hard to get the dose correct. Additionally, warfarin contributes to a third of hospitalizations for adverse drug reactions in people over 65 years of age in the USA.

Previous research has revealed that two genes, VKORC1 and CYP2CP, can account for about 30% of the difference in warfarin response in people of Asian and European descent. 

However, these genetic markers are less predictive of dosing regimens in African Americans.

In order to pinpoint additional genetic factors that control warfarin dose requirements in African Americans, the investigators examined health information and DNA samples from 533 African-American adults on stable doses of warfarin from the International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham.

After checking through a range of genomes, the researchers found that the strongest signals were clustered around the well-known VKORC1 and also found a significant link between the rs12777823 variant on chromosome 10 and warfarin dose. This result was verified in an independent cohort of 432 additional African American patients.

The outcomes suggest that African Americans who carry one or two copies of this polymorphism need a dose decrease of approximately 7-9 mg less per week compared to other patients.

Mark Alberts, from UTSW Medical Center in Texas, commented on the study saying:

"Use of genetic backgrounds to help to guide warfarin dosing has been advocated for several years by the US Food and Drug Administration... However, the practical aspects (and limitations) have not been fully appreciated. Genetic testing has several challenges: it is not widely available in some areas; it is costly; and clinicians often can identify the correct dose before test results are available. If these problems were corrected, the actual use of such tests might increase substantially."

Source: Medical News Today/Written by Kelly Fitzgerald