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Your Genes Can Affect Drug Activity

By Ed Edelson
HealthDay Reporter

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  • TUESDAY, June 15 (HealthDayNews) -- A study showing that an individual's genetic makeup affects the response to a cholesterol-lowering drug heralds a new medical discipline, researchers say: pharmacogenetics.

    It's not something that will change medical practice just yet, says Dr. Paul M. Ridker, chief of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital in Boston and lead author of a new study appearing in the June 16 Journal of the American Medical Association. But "over the next 10 years we will see a lot of studies of this kind that will help address the issue of how we treat our patients."

    "Burgeoning" is the word Ridker used for the field of pharmacogenetics, while Susanne B. Haga, project director of human genetics at the Center for the Advancement of Genomics, a private research group, said knowledge about the interaction between genes and drugs "is growing by leaps and bounds."

    Over the long run, said Haga, co-author of an editorial accompanying the report, "information on how genetic variation affects drug efficacy and drug safety will become a basic part of drug development." But right now, she said, "the commercial ability to test for these variations is not available."

    Still, the study "will be a real eye-opener for physicians and patients," Ridker said.

    He and his colleagues did detailed genetic studies of 1,563 people taking pravastatin (Pravachol), one of several statin medications being prescribed to lower cholesterol levels. The researchers looked for individual variations called single-nucleotide polymorphisms (SNPs) in genes that play a role in the metabolism of cholesterol and other lipids.

    One of those genes produces a molecule called HMG-CoA reductase. Two common and closely linked SNPs in that gene "were significantly associated with a 22 percent smaller reduction in total cholesterol and a 19 percent smaller reduction in LDL cholesterol following 24 weeks of pravastatin therapy," the report said.

    That gene-based reduced activity was found in about 8 percent of the people studied, Ridker said, adding that the finding was more or less expected.

    "We've known for some time that some patients get a greater reduction than others," he said. "We were looking for evidence that genetic variation played a role. We found it on the basis of genes that are the target of the drug itself."

    The finding doesn't call for any major change in treatment of patients with the specific SNPs, at least now, Ridker said. "It could well be that just a higher dose will overcome this problem," he said.

    What is important is that the effect of genetic variation on the effects of drugs used to treat cancer now has been verified for at least one drug used in cardiology, Ridker said. It's not known yet whether genetic variation acts in the same way on other statins, he said, and many more studies are needed to determine the role played by pharmacogenetics in drug therapy.

    "This paper is important because it is a first demonstration, but we are in no way there yet," Ridker said.

    More information

    A rundown on statins and other cholesterol-lowering drugs can be found at the American Heart Association.

    (SOURCES: Paul M. Ridker, M.D., MPH, director, Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Boston; Susanne B. Haga, Ph.D, project director of human genetics, Center for the Advancement of Genomics, Rockville, Md.; June 16, 2004 Journal of the American Medical Association)

    Copyright © 2004 ScoutNews LLC. All rights reserved.

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