November 14, 2005

Genes worsen effects of statin drugs: study

WASHINGTON (Reuters) - 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

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.