Contact: Carole Bullock
American Heart Association

Gene Detected That Decreases "Bad" LDL Cholesterol In Men May Cut Heart Disease Risk By 50 Percent

DALLAS, May 15 -- A gene that helps keep bad cholesterol at bay -- and may reduce heart disease risk by 50 percent -- has been discovered by researchers reporting in this month's Arteriosclerosis, Thrombosis and Vascular Biology:Journal of the American Heart Association.

A research group from the Karolinska Hospital in Sweden found that the variation in the gene called microsomal triglyceride transfer (MTP) protein was linked to low levels of low-density lipoprotein, or LDL, in a study of 184 healthy men. LDL is the form of cholesterol that helps create the fatty deposits that can clog blood vessels and cause a heart attack or stroke.

The gene for MTP provides the blueprint for production of the protein that helps assemble LDL. Individuals who carry two copies of the variant form of the gene had LDL cholesterol levels 22 percent lower than those who had one copy or no copies of the variant.

"This kind of reduction would correspond to 50 percent lowering of risk of future heart disease in a 40-year-old man," says the study's lead author, Dr.Fredrik Karpe, of the Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden.

Individuals who carry a double copy of the gene variant would have a 25 percent reduced risk.

"The variant of the MTP, found in six percent of the individuals, is of functional importance in regulating expression of the MTP and influences LDL cholesterol concentration," says Karpe. "These findings add to our understanding of how the LDL cholesterol level is regulated and suggest that genetic variation in the MTP expression may have important implications for the development of cardiovascular disease."

The MTP gene was cloned in 1993, but this is the first report on a common genetic variant within the gene. The variant changes the promoter region of the MTP gene. The promoter region acts like a start button that signals the gene to encode a protein. Individuals with the variant produce extra MTP, which results in an altered production of very-low-density lipoprotein (VLDL), a protein-coated fat that is necessary to make LDL.

The findings may have important implications in the field of drug development. Most drugs that treat high cholesterol work by removing excess amounts. However, the MTP variant helps reduce production of LDL.

Some drug companies have already begun looking at MTP inhibitors, to help lower LDL.

Even though the study was conducted in men, Karpe says the findings that individuals who carry the variant -- about six percent of the population --would be protected against heart disease would likely apply to women.

Dr. Karpe's co-authors are Bjorn Lundahl; Ewa Ehrenborg; Per Eriksson;and Anders Hamsten.

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