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Genetics May Hinder Some Cholesterol Drugs

Genetic Research Promises Better Treatments for High Cholesterol
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WebMD Health News

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.

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Your total cholesterol level is in the Desirable range, but your level of "bad" LDL cholesterol is Very High. This may mean that your level of high-density lipoprotein (HDL), or "good" cholesterol, is too low. It is best to have a high level of "good" HDL and a low level of "bad" LDL because the HDL helps keep your LDL level in check. Ask your doctor for your HDL level. If your HDL is low, increasing your physical activity can increase it, which may help reduce your LDL level.

Your total cholesterol level is Borderline High, but fortunately your level of "bad" LDL cholesterol is optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have other non-measured increases in LDL-like particles that can increase heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

Your total cholesterol level is Borderline High, but fortunately your level of "bad" LDL cholesterol is near optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have other non-measured increases in LDL-like particles that can increase heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

Your total cholesterol level is Borderline High. Your level of "bad" LDL cholesterol is Borderline High, too. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

Your total cholesterol level is Borderline High. Your level of "bad" LDL cholesterol is High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

Your total cholesterol level is Borderline High. But your level of "bad" LDL cholesterol is Very High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

Your total cholesterol is High, but your level of "bad" LDL cholesterol is optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have elevated secondary lipids, such as non-HDL particles that increase the risk of heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

Your total cholesterol is High, but your level of "bad" LDL cholesterol is near optimal. This could mean you have a high level of high-density lipoprotein, or "good" HDL cholesterol, which protects against heart disease. Or you could have elevated secondary lipids, such as non-HDL particles that increase the risk of heart disease. Your LDL level also could be optimal if you are taking a statin medication. Please check with your doctor to get your complete lipid profile and see if you may need additional treatment. In the meantime, find more information on WebMD's Cholesterol Health Center.

Your total cholesterol level is High. Your level of "bad" LDL cholesterol is Borderline High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels!

Your total cholesterol level is High. Your level of "bad" LDL cholesterol is High, too. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels! If you are struggling to bring down your total cholesterol and LDL cholesterol levels, your doctor may prescribe medication, such as statins. Following medication, dietary, and exercise instructions should result in improvements.

Your total cholesterol level is High, and your level of "bad" LDL cholesterol is Very High. Working to bring down your total cholesterol decreases your LDL cholesterol level. You can do this by exercising more and eating less food with saturated fats. Check food labels! If you are struggling to bring down your total cholesterol and LDL cholesterol levels, your doctor may prescribe statins or other cholesterol-lowering medications.

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