Scientists Parse Dna Tied To Heart Disease Susceptibility (5/7/2007)

In the May 3 issue of Science Express, an international research team - including scientists from two University of Texas health institutions - announced the discovery of a tiny stretch of DNA on chromosome 9 that increases individual susceptibility to heart disease by 30 to 40 percent, regardless of other established risk factors.

"We identified a region of the genome that is a significant predictor of heart disease," said Eric Boerwinkle, Ph.D., one of the study's coauthors and director of the Research Center for Human Genetics at UT's Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM). "I've been doing this my entire adult life and I've never seen a gene with this large an effect on heart disease. This is the largest contribution of any gene variants ever reported for heart disease."

The study was led by Ruth McPherson, M.D., Ph.D., an endocrinologist at Canada's University of Ottawa Heart Institute (UOHI), in collaboration with Jonathan C. Cohen, Ph.D., at The University of Texas Southwestern Medical School at Dallas.

McPherson, who also is a molecular biologist and director of UOHI's Lipid Clinic and Lipid Research Laboratory, is lead author on the study titled "A Common Allele on Chromosome 9 Associated with Coronary Heart Disease," which will be published in an upcoming issue of the journal, Science.

The findings could help geneticists identify people at risk of heart disease, enabling early preventive therapies, including lifestyle changes and medications to reduce risk, said Boerwinkle, who also is director of the Human Genetics Center at the UT School of Public Health and the Kozmetsky Family Chair in Human Genetics. The research could also lead to a better understanding of the biological pathways that lead to heart attack.

The study involved a research technique called genome-wide association scanning. Results were based on samples from more than 23,000 people in the United States, Canada and Denmark.

Using a map of genetic variants, researchers linked two variants, also known as single nucleotide polymorphisms (SNPs), to heart disease. They were found in a non-protein coding region of chromosome 9. "The SNPs were consistently associated with early onset heart attack, unrelated to many of the traditional risk factors for heart disease including diabetes and high blood pressure," Boerwinkle said.

To locate the variants responsible for coronary heart disease, researchers compared the SNPs in heart patients to the SNPs in healthy people, he said. They used population samples selected from the 2,765 participants in the Ottawa Heart Study, the 11,478 people in the Atherosclerosis Risk in Communities project (ARIC) and the Dallas Heart Study, and the 10,578 Danish men and women in the Copenhagen City Heart study. Boerwinkle is the principal investigator of the ARIC project.

"This is an important finding for several reasons," said UOHI's McPherson. "This is a common genetic variant which has a very strong effect on heart disease risk that isn't related to other factors that we already know about ... If we can identify genetic factors which influence heart disease risk over and above known risk factors, we can do a better job of identifying those people who will benefit most from early intervention to reduce their risk."

Coauthors of the study included: Nihan Kavaslar, Ph.D., Alexandre Stewart, Ph.D., Robert Roberts, M.D., all with the University of Ottawa Heart Institute; Cohen with Helen H. Hobbs, M.D., and Alexander Pertsemlidis, Ph.D., with the UT Southwestern Medical Center; Len A. Pennacchio, Ph.D., Lawrence Berkeley National Laboratory; Aaron R. Folsom, M.D., University of Minnesota; David R. Cox, M.D., Ph.D., and David A. Hinds, Ph.D., both with Perlegen Sciences; and Anne Tybjaerg-Hansen, M.D., Copenhagen University Hospital.

"Science Express" provides rapid electronic publication of selected research papers, perspectives and articles that have been accepted for publication in Science. Articles are available online at http://www.sciencemag.org/magazine.dtl

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

Post Comments: