Attacking Heart Disease at Its Genes

Some day, health professionals will have a fairly complete profile of the human genes that influence heart disease risk. Individuals could then adopt the habits most likely to reduce risk because different genes or combinations of genes respond differently to changes in diet, exercise, smoking, alcohol consumption or medications, such as cholesterol-lowering drugs.

One pioneer in this field is Jose Ordovas at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts in Boston. The center's research is funded by the Agricultural Research Service, USDA's chief scientific arm.

Ordovas focuses on genes that control blood lipids and has identified several of the 40 or so genes so far known to affect cardiovascular health. He estimates that hundreds of genes may ultimately go into a risk-analysis database.

Four main disorders under genetic control contribute to heart-disease risk: high blood lipids, high blood pressure, obesity in the abdomen, and impaired glucose tolerance, resulting in type II diabetes. Whether a disorder manifests itself depends upon an individual's lifestyle habits and age.

Moreover, one gene can affect another. For example, in an obese individual, an obesity gene can trigger a normally beneficial gene for blood lipids to express high LDL ("bad") cholesterol and triglycerides. But if the individual stays lean, the beneficial gene could prevail--all other things being equal.

Such genetic interactions have produced conflicting results in diet intervention studies and led to public confusion over the value of changing one's fat intake. The appropriateness of “one-size-fits-all” public health recommendations is being seriously questioned, according to Ordovas.

For example, people with a genotype known as APOE4 are prime candidates for diet therapy instead of cholesterol-lowering drugs, according to Ordovas. If these people follow the standard cholesterol-lowering diet, they can expect about a 30-percent decrease in LDL cholesterol. That's about the decrease expected from cholesterol- lowering drugs--except for people of the APOE4 genotype, who respond poorly to the best of these drugs.

A story about the research appears in the July issue of Agricultural Research magazine and on the web at:

/is/AR/archive/jul99/heart0799.htm

Scientific contact: Jose M. Ordovas, ARS Human Nutrition Research Center on Aging at Tufts University, Boston, Mass.; phone (617) 556-3102, fax (617) 556-3103, ordovas_li@hnrc.tufts.edu.