DNA Survey Reveals Nature's Way of Reducing Heart Disease

Major Genetic Findings Related to Heart Disease

First the good news and then the bad. As part of international teams of researchers, faculty members at two University of Texas health institutions have reported finding variations in a single gene that reduce the risk of heart disease. They also have discovered a tiny stretch of DNA on chromosome 9 that increases individual susceptibility to heart disease by 30 to 40 percent. Eric Boerwinkle, Ph.D., holder of the Kozmetsky Family Chair in Human Genetics at the UT Health Science Center at Houston, is a member of both teams.

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 appeared in the April issue of the journal Nature Genetics.

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. The most common type of fat in the bloodstream, triglycerides can cling to artery walls and restrict blood flow. Boerwinkle said that the data show that life-long reductions in plasma triglyceride levels can reduce the risk of heart disease.

The most common type of fat in the bloodstream, triglycerides can cling to artery walls and restrict blood flow. Boerwinkle said that the data show that life-long reductions in plasma triglyceride levels can reduce the risk of heart disease.

Personalized Therapy

“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 and chief executive officer 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 levels, said Boerwinkle, who also is director of the IMM’s Research Center for Human Genetics and holder of the Kozmetsky Family Chair in Human Genetics. When triglycerides go down, “good” cholesterol goes up and “bad” cholesterol goes down. “Bad” cholesterol is also a risk factor for heart disease.

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

“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.

Validated in Larger Studies

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

Stefano Romeo, Ph.D., postdoctoral fellow at the UT 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. Fu and Boerwinkle also hold faculty appointments in the UT Graduate School of Biomedical Sciences at Houston.

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 are from UT Southwestern Medical Center, Lawrence Berkeley National Laboratory, and Copenhagen University Hospital.

By Rob Cahill, Institutional Advancement