Attacking Heart Disease at Its Genes
July 23, 1999
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
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
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
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:
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,