Genetics May Hinder Some Cholesterol Drugs
Genetic Research Promises Better Treatments for High Cholesterol
June 15, 2004 -- For millions with high cholesterol, statin drugs like Lipitor have been lifesavers. But because of genetics, the drugs don't work for everyone, new research shows. The study paves the way for a new era of gene-based medicine, experts say.
Both the report and editorial appear in the latest issue of TheJournal of the American Medical Association (JAMA).
Statin drugs have shown that they can be highly effective in lowering high cholesterol -- both total and LDL "bad" cholesterol -- and reducing the risk of heart disease. Yet there has been wide variation in individual response to these drugs.
This newest study identifies genetics as a factor, finding that small variations of the gene that statins target control individual responses, writes lead researcher Daniel I. Chasman, PhD, with Brigham and Women's Hospital and Harvard Medical School.
Chasman's study introduces the science of pharmacogenetics -- tailoring drug treatments according to individual genetic profiles, writes Suzanne B. Haga, PhD, in an editorial.
His study is the first to demonstrate the impact of genetic variation for this popular class of drugs, Haga writes. It justifies the need for further study to improve treatment alternatives. Already-existing technology has the potential to tweak these commonly used drugs to make them more effective.
In Chasman's study, 1,536 adults with high cholesterol took 40 mg of Pravachol daily for 24 weeks. Blood samples were taken so their DNA could be analyzed for variations in 10 genes thought to affect cholesterol metabolism. These genes were then compared to see what effect the cholesterol-lowering drug had on blood cholesterol levels.
"We found two common and closely linked ... genes that were significantly associated with a 22% smaller reduction in total cholesterol and a 19% smaller reduction in LDL cholesterol," writes Chasman.
The authors write that in terms of an absolute difference in total cholesterol reduction, the effect from these variations is large enough to affect health on a population basis.
Whether this genetic variation can be offset remains to be seen, he writes. Until a gene-based therapy is available, doctors might try adjusting the drug dosage or using a different cholesterol-lowering drug.
Since his study only involved Pravachol, it's difficult to tell whether this genetic variation applies to other statins used to treat high cholesterol, writes Chasman.