November 15, 2005

Genes Worsen Effects of Statin Drugs — Study

WASHINGTON -- U.S. researchers said on Monday they may have made progress toward explaining why statin drugs, which lower cholesterol, do not work as well in some people as in others -- especially blacks.

They found two variations in a gene involved in the body's own production of cholesterol appeared to make statin drugs work less effectively.

The finding, reported at a meeting of the American Heart Association in Dallas, could help in the development of more tailored treatments in the future.

"This study is one piece of the overall equation that we and others are trying to fill in to understand why some people do not respond as well as others to statin therapy," said Dr. Ronald Krauss, director of atherosclerosis research at Children's Hospital Oakland Research Institute in California, who led the study.

For the study, Krauss and colleagues tested the DNA of 296 black Americans and 573 whites, all of them typical high cholesterol patients who would normally be prescribed statin drugs.

Krauss' team found nine variations of the gene that carries the code for HMGCoA reductase, the enzyme that statin drugs target to reduce the body's production of cholesterol.

Of these nine variations, known as haplotypes, two were associated with a reduced response to statins.

For instance, the 35 blacks who carried haplotype 7 and who took statins did not see their low density lipoprotein (LDL or "bad" cholesterol) go down as much as did the others in the study. The same effect was not seen in whites with haplotype 7.

The 10 volunteers with both variations had a much lower response to statins. Their LDL went down only 24.5 percent compared to nearly 42 percent among the others. This combination was seen in nine of the blacks and just one of the whites in the study.

The finding does not yet suggest that patients should be gene-tested and kept off statins if they happen to carry one of the two mutations, Krauss said.

"This is just one gene and two haplotypes, and there are certainly many more genes involved. But an understanding of the basis for these genetic differences in statin response could lead to improved treatments for reducing LDL levels," he said.