Dna Survey Reveals Nature's Way Of Reducing Triglycerides And Heart Disease (4/27/2007)

Eric Boerwinkle, Ph.D., Kozmetsky Family Chair in Human Genetics, UT School of Public Health, in his lab. - Photo Credit: University of Texas

If you're one of the lucky few with variations in a single gene that reduce artery-clogging triglycerides in your blood, you have an increased chance of avoiding heart disease, the leading cause of death in adult Americans. That's the good news from a DNA study that involved scientists from two University of Texas health institutions and led to the discovery of these genetic variations in approximately 3 to 4 percent of the people tested.

If not, you may still one day benefit from efforts by researchers to mimic the effects of these variations. In the meantime, a healthy diet and exercise are good ideas for everyone.

The study, "Population-based Resequencing of ANGPTL4 Uncovers Variations that Reduce Triglycerides and Increase HDL," appears in the April issue of the journal Nature Genetics.

Triglycerides are the most common type of fat in the bloodstream, and they can cling to artery walls and restrict blood flow.

Eric Boerwinkle, Ph.D., a co-author of the study and director of The University of Texas School of Public Health's Human Genetics Center, described the variations as "nature's way" of reducing triglycerides. "If you could develop an inhibitor to do this, you may be able to reduce triglycerides in the blood and reduce the risk of heart disease," he said.

Boerwinkle said that the data show that life-long reductions in plasma triglyceride levels can reduce the risk of heart disease.

"The research in cardiovascular disease is seeking the identification of genes responsible for an individual�s disease risk," said C. Thomas Caskey, M.D, director, chief operating officer and director-/CEO-elect of the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM). "Discoveries such as Dr. Boerwinkle's will ultimately lead us to an ability to personalize the therapy based on the individual's specific disease risk gene. More is expected from this strategy."

Another benefit of these genetic variations is improved cholesterol, said Boerwinkle, who also is director of the IMM's Research Center for Human Genetics. When triglycerides go down, "good" cholesterol goes up and "bad" cholesterol goes down. These are also risk factors for heart disease.

The study involved a gene called Angiopoietin-like 4 (ANGPTL4) that is associated with triglyceride levels in genetically modified mice and a population-based probability sample of Dallas County residents, Boerwinkle said.

Using blood samples provided by the 3,551 participants in the Dallas Heart Study, scientists tested the ANGPTL4 gene in these individuals for sequence differences and ranked the blood triglyceride levels of participants in quartiles. Thirteen unique sequence differences were identified in the bottom quartile of triglyceride levels and only two in the top. Ten of the 13 differences were detected in European Americans.

"This is the first time a gene has been sequenced in a large sample and related to disease in that sample," Boerwinkle said. Previous large-scale sequencing efforts have focused on only a small number of people with a certain disease.

These data demonstrate the utility of medical resequencing for understanding the genetic basis of complex traits - such as triglyceride levels - and are "only the tip of the iceberg," Boerwinkle said.

The research team is sequencing other genes with similar goals in mind.

The genetic associations observed in the Dallas Heart Study were validated in two larger population studies, the Atherosclerosis Risk in Communities study (15,792 subjects) and the Copenhagen City Heart Study (10,135 subjects).

Stefano Romeo, Ph.D., postdoctoral fellow at The University of Texas Southwestern Medical Center at Dallas, was lead author on the Nature Genetics study.

Yunxin Fu, Ph.D., the Betty Wheless Trotter Professor in Medical Sciences at the UT School of Public Health�s Human Genetics Center, also contributed to the study.

"This study demonstrates the importance of collaboration in modern biomedical research and how Texas has the opportunity to lead the way in such collaborative efforts," Boerwinkle said.

The study was supported by grants from the Donald W. Reynolds Foundation, the National Institutes of Health, the Danish Medical Research Council, the Danish Heart Foundation and the Research Fund at Rigshospitalet (Copenhagen University Hospital).

Additional co-authors include: Helen H. Hobbs, M.D., and Jonathan C. Cohen, Ph.D., both with the UT Southwestern Medical Center; Len A. Pennacchio, Ph.D., Lawrence Berkeley National Laboratory, Berkeley, Calif.; and Anne Tybjaerg-Hansen, M.D., Copenhagen University Hospital.

Note: This story has been adapted from a news release issued by the University of Texas

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