Gene Variant Keeps Blood Triglyceride Levels Low

And it's much more common in whites than blacks, research shows

MONDAY, Feb. 26, 2007 (HealthDay News) -- About 3 percent of Americans of European descent have lucked out, genetically speaking, when it comes to keeping blood fats called triglycerides at bay.

New research shows that a rare variant of a particular gene called ANGPTL4 appears to help keep these dangerous fats at low levels, while boosting levels of HDL "good" cholesterol.

While the finding doesn't have immediate implications for treatment or prevention of heart disease, it does give scientists new insights into arterial health.

"This helps us understand the underlying biology, which may lead to an array of different ways to approach high triglycerides or other factors," said Dr. Eric Rimm, an associate professor of epidemiology and nutrition at the Harvard School of Public Health, who was not involved in this study but has done similar work. "This one gene is a small piece of a larger puzzle that may help us target not just treatment, but also dietary advice or lifestyle factors in better ways."

The study, which was led by Jonathan Cohen, of the University of Texas Southwestern Medial Center at Dallas, was published in the Feb. 25 issue of Nature Genetics.

Triglycerides are essentially microscopic bits of fat floating in the bloodstream. Eventually, Rimm said, they pass through the liver and turn into LDL "bad" cholesterol, so keeping triglyceride levels down is important to cardiovascular health.

Some people are blessed, however, by a natural ability to do so, and Cohen's team sought to understand why. They zeroed in on ANGPTL4, a gene they already suspected might have links to triglyceride metabolism.

Using high-tech genetic analyses, they compared particular variants of this gene in more than 3,500 adult participants enrolled in the Dallas Heart Study.

The team found 93 separate variants, but noted that one in particular -- E40K -- "was associated with significantly lower plasma levels of triglyceride and higher levels of high-density lipoprotein (HDL) cholesterol," the so-called "good" cholesterol.

The E40K variant was also much more likely to be found in Americans of European descent -- close to quadruple the rate seen in black Americans, the researchers found. These findings were replicated in a Danish study, as well.

The discovery, while important, doesn't explain long-recognized disparities in heart disease between blacks and whites, experts said.

"There are probably so many factors involved in that, that just one gene isn't going to answer all of our questions," said Dr. Daniel Fisher, a cardiologist at New York University Medical Center.

Rimm agreed. He said that racial differences in heart disease are likely to be based, in part, on variants in a wide number of genes, not just one. "There are cultural differences, too, in how people live," he said.

And he was doubtful that any immediate clinical benefit would spring from the Dallas finding. Rimm pointed out that, at this point in time, Cohen's group can only speculate on how E40K might lower triglyceride levels.

Still, this type of DNA-based research will pay off in the long run, said Rimm, whose team at Harvard has also spotted a variant gene that seems to protect carriers against type 2 diabetes and heart disease. That discovery was published last April in the Proceedings of the National Academy of Sciences.

"It might be that in 15 or 20 years, we'll come up with a set of genes that we can then use to say, 'OK, these people with these 15 variants are going to have higher triglycerides, so we'll focus on specific diets or training programs for them,' " he said.

"So, you have this vision of something from Star Trek where someone walks in with a scanner and says, 'Yes, you need this, and this and this,' " Rimm said. "Eventually, it could come to that. But I think that, for now, this just helps us understand mechanisms as to why people have higher or lower triglycerides."

More information

There's more on triglycerides at the American Heart Association.

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