Gene may increase risk for heart disease
October 22, 1999
Web posted at: 3:20 p.m. EDT (1920 GMT)
By Christine Cosgrove
(WebMD) -- Geneticists have located a gene that may be responsible for increasing the risk of heart disease. The gene, called ABC1, normally helps rid the body of cholesterol by maintaining sufficient levels of "good" cholesterol, also known as high density lipoprotein (HDL). But when mutated, the gene can no longer maintain levels of HDL, the researchers said Thursday at the 49th annual meeting of the American Society of Human Genetics in San Francisco.
Michael Hayden, one of the lead researchers and a professor of medical genetics at the University of British Columbia, said the study revealed that people with this genetic defect who have low HDL levels are at just as much risk for heart disease as people with high levels of low density lipoprotein (LDL), commonly called "bad" cholesterol.
Improved coronary artery treatment
The findings could eventually lead to a drug that would provide physicians with a way to treat people with coronary artery disease -- about one-half of whom have low levels of HDL, said Hayden, adding that coronary artery disease is the leading cause of death in Western industrialized and developing countries.
In the past 10 years, drugs known as statins have been developed to lower LDL, which picks up cholesterol from the liver and delivers it to the cells -- or onto the walls of the arteries where there is potentially too much cholesterol already for the cells to absorb. But understanding how to increase levels of HDL, which removes excess cholesterol from the bloodstream and takes it to the liver where it is excreted, has eluded researchers.
"The excitement here is that we've known so little about genes that are involved in HDL formation," Hayden said at a press conference at the meeting. "We know a lot about how cholesterol gets into cells, but very little about how cholesterol gets out of cells."
How the gene was found
A rare genetic disorder called Tangier Disease provided the clue to the gene's discovery. Individuals with this disorder have very low HDL levels and frequently suffer from coronary artery disease earlier in life than most other patients. Last year, German biochemist Stephan Rust and colleagues at the Institute of Arteriosclerosis Research, University of Munster, found that the cause of Tangier disease was due to a gene on chromosome nine.
Rust, researchers from Canada and Hayden all found the location on the chromosome, leading to the identification of the ABC1 gene. Angela Brooks-Wilson, director of human genetics at Xenon Bioresearch, a biotechnology company in Vancouver, British Columbia, also contributed to the study.
Another region on the chromosome may also be responsible for lower HDL levels, said John Blagero, a statistical geneticist from the Department of Genetics at the Southwest Foundation for Biomedical Research in San Antonio. Studying large families of Mexican-Americans, Blagero found that the chromosome somehow affects HDL levels in those families, which also have higher-than-normal rates of diabetes. Diabetes is associated with higher risk for heart disease, Blagero said at the press conference.
The researchers agree that more than one gene may be responsible for low levels of HDL. Blagero said he suspects that another gene located on chromosome seven may be working with ABC1 to lower levels of HDL in the Mexican-American families he examined.
The therapeutic outlook
Identifying ABC1 is a big step in tracing the pathway that links low HDL to the development of atherosclerosis, the hardening of the arteries that leads to heart disease, the researchers said.
"We are very hopeful that this will eventually lead to a major therapeutic strategy," said Harald Funke of the Institute for Arteriosclerosis in Munster. "The discovery of the LDL receptor pathway about 10 years ago eventually led to the development of the statin drugs, which are the largest selling drugs in the world."
Last year, sales of statin medications totaled about $16 billion, Funke said. Development of a treatment based on the recent findings will take about 10 years, the usual time required to develop a new medication.
Copyright 1999 webmed, Inc. All rights reserved.
RELATEDS AT :
High cholesterol levels
Human gene research
American Society of Human Genetics
American Heart Association
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