Patients with a certain genetic variation and who received the antiplatelet drug clopidogrel — Plavix — had a decreased platelet response to treatment, revealed by researchers.
Researchers at the University of Maryland School of Medicine have identified a common gene variant carried by as many as a third of the general population that is believed to play a major role in determining why people do not respond to a popular anti-clotting medication, Plavix.
If the medication doesn’t work, patients are at increased risk for subsequent heart attacks, strokes and other serious cardiovascular problems.
The results of the study, published in the Aug. 26, 2009, issue of the Journal of the American Medical Association (JAMA), confirm a previously reported link between people’s decreased response to Plavix, also known as clopidogrel, and common variations of the CYP2C19 gene. The study is the first to identify a common variant of this gene by using a sophisticated technique called a genome-wide association study to rapidly scan hundreds of thousands of genetic markers in the DNA of participants. More than 400 members of the Old Order Amish community in Pennsylvania took part in the study.
“By scanning the entire genome, we found compelling evidence that the CYP2C19 gene is a key determinant of how people respond to this medication,” says the lead author, Alan R. Shuldiner, M.D., professor of medicine and director of the Program in Genetics and Genomic Medicine at the University of Maryland School of Medicine in Baltimore. “We didn’t detect any other common gene variants that appear to be as significant as CYP2C19, but our research suggests that people’s response to clopidogrel is largely inherited and additional common and rare gene variants most likely are involved.”
Dr. Shuldiner says he will continue his research to search for these gene variants. “The more we know about how genes affect people’s response to medicines, the better able we are to develop effective new therapies and tailor treatment to an individual patient’s genetic make-up,” he says.
About 30 percent of the general population in the United States has the CYP2C19 variant identified in the study. Dr. Shuldiner says that it can be detected by a simple genetic test using DNA from blood or saliva. “If people have the gene variant, they might need to take a higher dose of clopidogrel or a different medication altogether,” he says, adding that more research is needed before such testing becomes routine.
Plavix is one of the world’s best-selling medications. It is used to prevent platelets from sticking together and causing blood clots in patients with cardiovascular disease who are at risk of having future heart attacks and strokes.
Source: University of Maryland Medical Center, USA