Medical researchers have discovered an abnormal gene that predisposes some people to heart disease, the nation's most common killer, and have developed a test that could someday be used routinely to identify healthy people carrying the gene.
Doctors have long suspected that hereditary factors played a role in heart disease, but the new discovery is the first to link a propensity to the disease with a specific, common genetic defect.
About one-third of the people under 60 who already have coronary artery disease carry the defective gene, the scientists found. By comparison, the defect is present in only about 3 percent of those with no sign of heart disease.
Although it may be several years before the test is generally available, the researchers hope that eventually young people who learn they are carrying the defect will have a powerful motivation to adopt low-fat, moderate-exercise, no-smoking habits that can improve their chances of avoiding heart disease.
The discoveries were reported in yesterday's New England Journal of Medicine by a team from the United States, Canada and Italy.
"We think this test could prove to be a more reliable predictor of the risk of heart disease than anything else we have at the moment," said Ernst J. Schaefer who, with Jose M. Ordovas, led the scientists. Both work at the Agriculture Department's nutrition research center at Tufts University in Boston. Their chief collaborator was Sotirios K. Karathanasis of the Harvard University Medical School.
It is not clear how the genetic defect works, but the result is to prevent the body from making enough of a normal substance in the blood that removes excess cholesterol deposits from artery walls.
When cholesterol gets too thick inside the coronary arteries supplying the heart muscle, the supply of oxygen is pinched off and severe chest pains can result. Also, the narrowed arteries are highly vulnerable to a heart attack if a blood clot suddenly blocks the opening.
Cholesterol is an essential, fat-derived substance. It is carried in the bloodstream by two related molecules, both made of a combination of fat, or lipid, and protein -- low density lipoprotein (LDL) and high density lipoprotein (HDL). LDL tends to deposit cholesterol on artery walls, and HDL tends to remove it.
Normally there is a balance between the two forms so that cholesterol does not build up. However, doctors have known for about 10 years that some people have unusually low levels of HDL and develop clogged arteries relatively early in life, especially if they eat a diet rich in cholesterol. In severe cases such people may have heart attacks in middle age. It is also known that this condition runs in families.
The balance of HDL and LDL can vary for many reasons, but the new findings, Schaefer said, show that the defect is a mutation of the genetic message that somehow governs the production of HDL's main ingredient, a protein known as A-I. The defect inhibits the gene's ability to make the protein.
In the string of genes that make up one particular chromosome, number 11, the defect lies almost immediately adjacent to A-I gene.
Molecular biologists know that every gene that carries the code for a specific protein can work only at rates governed by neighboring sequences of genetic code.
The new test for the regulatory defect is done on the genes carried in white blood cells. Schaefer said that several years of testing would be required to be certain of its predictive value but that, if the early results held up, the test might be commercially available in about five years.