Study helps explain wide response to statins

By Julie Steenhuysen

CHICAGO (Reuters) - Differences in the way people process genetic information may explain why some get a huge benefit from cholesterol-fighting drugs known as statins, while others get very little, U.S. researchers said on Monday.

Statins are the world's top-selling drugs and are highly effective at cutting the risk of heart attack and stroke.

"We know not everybody who takes statins has the same benefit. We've been looking at the possibility that genetic differences contribute to that variability," said Dr. Ronald Krauss of the Children's Hospital Oakland Research Institute in California, whose study appears in the journal Circulation.

His team found that an aberration in the way a single enzyme was made helped to explain 9 percent of cases in which people saw little benefit from statins.

The enzyme, known as HMGCR, is central to the production of cholesterol. Statins reduce LDL, or low-density lipoprotein -- the so-called bad cholesterol, by blocking this enzyme.

"What we discovered is there is in everyone the ability to process the HMGCR gene in a way that causes a different form of the enzyme to be produced," Krauss said in a telephone interview.

While genes carry the basic genetic information for making proteins, how the body interprets that information -- through a process known as alternative splicing -- seems to make a big difference, he said.

"It's the basic recipe, but the ingredients can be shifted around and you get a different flavor," Krauss said.

For this study, Krauss and colleagues analyzed differences in how the gene responsible for producing HMGCR was processed or spliced among more than 900 participants enrolled in a cholesterol study. People in the study took a 40 milligram dose of simvastatin, a statin developed by Merck & Co under the brand name Zocor, which is now available generically.

The researchers found that an enzyme produced the normal way can be strongly inhibited by statins. But people who had an aberrant form were more resistant to statins.

"As much as it is a big piece of the puzzle that could help us understand why some people don't do as well, it is not by any means the whole story," Krauss said.

He said the finding adds to prior studies about the genetic factors that influence the response to statins.

"We know there is a complex set of machinery that is involved in the splicing process. We'd like to understand better how that is regulated in the case of this particular gene," Krauss said.

That could lead to better drugs, and may even lead to genetic tests that would help guide treatment, he said.

(Editing by Will Dunham)