Fat in Blood Tied to Gene

Triglyceride governor may be new heart disease risk factor

THURSDAY, Oct. 4, 2001 (HealthDayNews) -- Mining the newly published map of the human genome, researchers have identified a hitherto unknown gene that appears to play an important role in determining an individual's risk of heart attack and stroke.

The gene governs blood levels of triglycerides, a family of fats that rank with cholesterol as potential components of the deposits that clog arteries, says a report in the Oct. 5 issue of Science by researchers at the Lawrence Berkeley National Laboratory in California. They have identified variations, or alleles, of the gene that make the formation of artery-clogging deposits either more or less likely.

The discovery someday could be used in a test to identify people at high risk of heart disease and stroke, they say.

The discovery was made first in a study of the mouse genome, which has strong similarities to the human genome, says lead study author Len A. Pennacchio, a postdoctoral fellow at Lawrence Berkeley. A close look at a mouse chromosome that carries a well-known cluster of genes that influence blood lipid -- fat -- levels showed the presence of the particular gene. The researchers then looked at the corresponding human chromosome and found the same gene.

"From our data, it appears to be a really strong contender as a determinant of risk," says Pennacchio.

Some data come from genetically engineered mice, in which the gene's activity was found to have a strong effect on blood triglyceride levels. That finding has been confirmed in human studies that compared blood triglyceride levels with different forms, or alleles, of the gene.

"In two different, independent studies, different alleles were found to contribute to higher levels of triglycerides," Pennacchio says.

One study was done by Dr. Ronald M. Krauss, head of the department of molecular and nuclear medicine at the University of California at Berkeley. His group used blood and gene samples from 500 participants in a long-term study of diet and heart disease.

"Of those 500, we found that about 10 percent of the individuals have one of several variants of the gene," Krauss says. "And lo and behold, the variations show a strong relationship with blood triglyceride levels, consistent with what was found in the animal studies. This is an important confirmation that the gene is associated with blood triglyceride levels."

Pennacchio says, "What needs to happen now is that more groups come out and replicate our findings. Other sample populations need to be looked at," he says.

Several research groups are doing that work, says Dr. Edward M. Rubin, head of the genome sciences department at Lawrence Berkeley. "They are using some of the markers that we have generated to see if there is any association with gene parameters and heart disease. In the next six months people should be able to tell if there is an association."

Krauss says, "The potential is clearly there. There is a long way to go to decide how genetic testing can be used to determine risk, but certainly this gene will be right up there."

What To Do

While genetic research goes on, the wisdom of a prudent diet, low in fat and high in fruit and vegetables, remains constant.

For information about triglycerides and their role in heart disease, go to the American Heart Association. The National Heart, Lung, and Blood Institute has a few pages to educate you about cholesterol.

SOURCES: Interviews with Len A. Pennacchio, Ph.D., postdoctoral fellow, and Edward M. Rubin, M.D., head, genome sciences department, Lawrence Berkeley National Laboratory, Berkeley, Calif., and Ronald M. Krauss, M.D., head, department of molecular and nuclear medicine, University of California, Berkeley; Oct. 5, 2001, Science
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