Medicine Gets Personal: Blacks Who Carry Genetic Variant May Need Lower Doses Of Blood Thinner

Blacks May Need Lower Dose Of Warfarin
A new study suggests a genetic marker more common among blacks indicates a lower tolerance for the blood thinner Warfarin. Creative Commons

The discovery of a genetic variation in some blacks that affects response to the blood thinner warfarin may improve the safety and efficacy of the drug, as the era of personalized medicine approaches.

The needed dose of warfarin for blacks with the genetic variation is significantly lower than for those without it, the researchers reported online Tuesday in The Lancet.

"Adding this genetic marker — found in more than 40 percent of African-American patients in the study — to standard dosing algorithms improved the predictability of warfarin dosing by 21 percent in these individuals, which has the potential to increase the safety and effectiveness of this notoriously hard-to-dose drug," Julie Johnson, professor of pharmacy at the University of Florida, said of the study she led.

Warfarin was first introduced in the United States in 1948 as a pesticide but was approved by regulators in 1954 as an anticoagulant for the prevention of thrombosis and embolism, or blood clots, resulting from many disorders — and is today used for both.

The drug is widely used to prevent blood clotting in patients following major surgery or those with a type of irregular heartbeat called atrial fibrillation, and also in patients with a history of blood clotting. But physicians sometimes have trouble determining the right dose for individuals.

Previous research identified two genes associated with approximately 30 percent of the difference between warfarin response in people of European and Asian ancestry, both of which applied less to blacks. In this study, investigators analyzed health information and DNA samples from hundreds of African Americans and found a strong association between the "rs12777823" variant on chromosome 10 and the drug dose.

Blacks with one or two copies of this variant require approximately 7-9 milligrams less per week than other patients, the researchers said.

Ideally, clinicians would employ personal genomic testing to properly tailor the drug to the patient, given that eyeballing one's skin color is no way to identify the genetic variants. The U.S. Food and Drug Administration is pushing for the use of such genetic backgrounds to help inform the dosing of warfarin, Mark Alberts, of the University of Texas Southwestern Medical Center, wrote in an editorial. "However, the practical aspects [and limitations] have not been fully appreciated."

Presently, personal genomic testing for warfarin dosing is limited by expense and availability and by the fact that clinicians often correctly determine the correct dosing before test results become available.

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