Clinicians have long thought that many Alaska Native people need lower doses of the blood-thinning drug warfarin (Coumadin®) than the general U.S. population. Now they know why.
A University of Washington-led team has identified two gene variants in Alaska Native people that have not been seen in other populations. Variants were found in the CYP2C9 gene, which encodes one of the enzymes needed to break down warfarin, said first author Dr. Alison Fohner. She conducted the research as part of her PhD thesis in Public Health Genetics at the UW School of Public Health.
Warfarin is used to treat people at risk for heart attack or stroke and is commonly used after major surgery to prevent blood clotting. Too much of it in the bloodstream can cause excess bleeding. (Bad reactions to prescription drugs is a leading cause of emergency room visits.)
“Genetic variation can affect how well a drug works for someone, and whether he or she will have serious side effects from that drug,” Dr. Fohner said. “Most of this type of research has been conducted in Caucasian people, and because genetics varies with ancestry, improvements to medical care that result from this research preferentially benefit Caucasians. Studies that include people from minority populations are needed so that all people can receive the benefits of genetic research.”
More than 700 Alaska Native people from across Alaska participated in this study. Researchers looked for changes in five genes known to be involved in the way warfarin works, especially looking for changes that were unique to Alaska Native people. Then, they looked at how commonly these changes were found in the Alaska Native population.
The study was published in the July issue of Pharmacogenetics and Genomics. The research was carried out with the Center for Alaska Native Health Research at the University of Alaska Fairbanks and with the Southcentral Foundation in Anchorage. Senior author was Dr. Kenneth Thummel, professor and chair of the department of pharmaceutics, adjunct professor of environmental and occupational health sciences, and deputy director of the Institute of Public Health Genetics.