ScienceDaily (Nov. 11, 1998) — DALLAS, Nov. 10 -- A gene that influences blood cholesterol levels can also predict how much those levels are affected by weight gain, smoking and other lifestyle factors, according to a study presented today at the American Heart Association's 71st Scientific Sessions.

Sathanur R. Srinivasan, Ph.D., and colleagues at the Tulane Center for Cardiovascular Health, New Orleans, showed that the gene called apolipoprotein E, or (apo)E gene, is influenced from childhood to adulthood by environmental factors.

An adult's blood cholesterol level can be influenced by the (apo)E gene -- which is expressed in three forms, or alleles: E-2, E-3 and E-4.

One form, the E-2, is associated with low levels of cholesterol. Cholesterol is a fatty substance in the blood that collects in the walls of blood vessels. If the blood vessels to the heart become narrowed -- a process called atherosclerosis -- a heart attack can result.

However, a new study shows that weight gain and other risk factors for heart disease cause cholesterol levels to rise relatively more in people with the E-2 form of the gene when compared to those with other forms of the gene. "People with E-3 or E-4 still may have elevated cholesterol levels if they gain weight, but the changes in E-2 individuals are greater," says Srinivasan.

"The (apo)E gene influences not only cholesterol levels from childhood to adulthood, but also moderates how an individual's cholesterol levels may interact with the risk factors and behaviors that contribute to heart disease," says Srinivasan. "Although people with the E-2 variant have this beneficial cholesterol profile, smoking, obesity and other cardiovascular risk factors can negate this benefit.

"The study shows that if you know your (apo)E gene type, it is possible to determine your risk status for high cholesterol during life and how great your risk can be influenced by factors such as smoking and decreases or increases in body fat," says Srinivasan.

Currently the test for (apo)E genes is only used in genetics laboratories and is not available to the general public.

The findings came from the Bogalusa Heart Study, based at Tulane University Medical Center, which followed 1,520 men and women for 16 years, starting when they were between the ages of five and 14. The scientists periodically measured blood levels of cholesterol and triglycerides (a common type of fat in the blood) and collected data on the participants' height, weight and lifestyles (smoking, alcohol use and oral contraceptive use).

People who inherited one copy of the E-2 form were found to have low blood levels of the low-density lipoprotein (LDL), the so-called "bad" cholesterol that promotes atherosclerosis, and high levels of high-density lipoprotein (HDL), called the "good" cholesterol because it helps remove LDL from the blood. People with low LDL levels and high HDL levels are at low risk for heart disease. About 10 percent of the population carries at least one copy of this form of the gene as part of their (apo)E combination, say researchers.

On the other hand, people who have inherited one copy of the E-4 form tend to have higher blood levels of LDL, placing them at greater risk for heart disease. Scientists say that roughly 20 percent of the population carries the E-4 form. Individuals with two copies of (apo)E-3, about 70 percent of the population, tend to have blood cholesterol levels that fall in the normal ranges -- between the cholesterol levels of those who have one copy of either E-2 or E-4. Co-authors are Abdalla Elkasabany, M.D.; Christian Ehnholm, M.D., and Gerald S. Berenson, M.D.

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