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Genes hold the key to our heart

Scientists track down 95 DNA regions associated with cholesterol and triglyceride levels, a finding that could lead to new treatment options with further research.

August 05, 2010|By Rachel Bernstein, Los Angeles Times

Heart health depends in no small part on diet and exercise, but genes are also crucial. Now, scientists involved in a massive genetic study have come a step closer to understanding the role of the latter, identifying 95 DNA regions associated with cholesterol and triglyceride levels.

Of those regions, 59 had not previously been identified and may, with further research, lead to new treatment options.

"It's a goldmine of new discovery," said Dr. Daniel Rader, a geneticist at the University of Pennsylvania medical school and coauthor of two new studies on the research. Both were released online Wednesday in the journal Nature.

Because the findings were based on genetic information gathered from more than 100,000 people, researchers were able to identify subtle variations that could potentially affect heart health. Such variations hadn't been visible in previous, smaller studies.

Differences within these regions explain 25% to 30% of the inherited portion of cholesterol and triglyceride levels across many ethnicities, including people of European descent, African Americans and East and South Asians, researchers said.

"It's the first step toward a better understanding of cholesterol metabolism," said Dr. Alan Shuldiner, a geneticist at the University of Maryland School of Medicine who was not involved in the research.

In most cases, the specific genes that affect cholesterol and triglycerides have not been identified, simply the larger regions of DNA in which they're located. The next step is to find the actual genes and figure out how they work. In the long run, such research could lead to new ways to treat people for high cholesterol or detect who may be at risk for heart disease.

The researchers, from a variety of institutions and universities, did identify four specific genes that could directly affect lipid levels. Highlighting the potential of further study, they found that one particular gene is involved in a previously unknown metabolic process that can lower bad cholesterol.

As for the broader regions identified in the new studies, they likely contain just a portion of the few hundred total genes that are probably involved in regulating cholesterol levels, said Harvard Medical School geneticist Dr. Sekar Kathiresan, who led the studies. The team is continuing to gather more research subjects to provide a larger pool for tracking down all the genes involved.

"My hypothesis is that, in three to five years, we will have a full tally of the genes," he said. "Then the question will be: What specific genes when targeted with drugs will actually help patients down the road? Having a full list of a few hundred, is that going to be like drinking from a fire hose?"

Cross-referencing the genes to find those that are also associated with coronary artery disease or heart attack could help narrow down the field, he said.

rachel.bernstein@latimes.com

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