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American Heart Association journal report:
Gene increases cholesterol levels in African-American men

DALLAS, May 12 -- A form of a gene found in some African-American men is associated with higher levels of cholesterol than other forms of the gene, a research team reports in this month's Arteriosclerosis, Thrombosis, and Vascular Biology: Journal of the American Heart Association.

The researchers studied the effects of three common forms of a gene called MTP. Black men with the "TT" form had significantly higher levels of total cholesterol, "bad" LDL cholesterol, triglycerides, and apolipoprotein B (ApoB) -- a protein that transports certain lipids (fats) in the bloodstream -- than black men with the other two forms of the gene.

Suh-Hang Hank Juo, M.D., Ph.D., lead author of the study, says, "Understanding the role of the TT gene variation could help researchers better understand what causes elevated cholesterol in the general population and may help in dealing with its potential consequences.

"We could target individuals carrying this gene, so they could get an early start on prevention," Juo says. "A person with the 'bad' form could try to lower the risk by exercising, eating a low fat diet, not smoking and taking medication to lower cholesterol."

Researchers studied African Americans because their cholesterol and other blood fat levels are different from Caucasians and they have a higher incidence of cardiovascular diseases than the white population, says Juo, an associate research scientist at Columbia University Genome Center in New York City.

For their study, the team used information collected from 586 young African-American men participating in CARDIA (Coronary Artery Risk Development in Young Adults) study. This long-term study at medical centers in Birmingham, Ala., Chicago, Minneapolis, and Oakland, Calif., has collected 10 years of data on more than 4,000 black and white men and women.

As part of the study, participants received a complete evaluation of their blood cholesterol every two years. Juo and his colleagues used blood drawn from the men in their study to determine which variation of the MTP gene each carried.

Genes exist in pairs. One gene is inherited from the mother and the other from the father. A person with the TT variant of the MTP gene inherited a T variant of the gene from each parent. In this study, 7 percent of the African-American men had this form, a prevalence quite similar to that found among white men in other studies.

Some research indicates that the gene plays an important role in directing the assembly of a particle that carries "bad" LDL cholesterol.

The team examined the lipid data from the men's five examinations over 10 years and found significant differences between the TT and other gene forms. The men with the other variations had very similar lipid levels. However, in the five exams, total cholesterol levels for the TT group ranged from 6 percent to 11 percent higher and LDL cholesterol was 8 percent to 15 percent higher than for the other two groups. High levels of cholesterol and triglycerides are often found together.

When the team statistically controlled for factors known to influence lipid levels--such as cigarette smoking, age, body weight, alcohol intake and exercise--they found the TT group still had significantly higher lipids compared to the men with the other two MTP variations. "This means the higher lipid levels are a pure genetic result," Juo says.

This study suggests that the TT variant could increase cardiovascular risks and could be important in understanding the genetics of heart disease. While the gene can be easily measured in a laboratory, Juo says the study findings must be confirmed by other researchers before recommending testing for the gene in larger populations.

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Co-authors are Zhihua Han, Ph.D.; Jonathan D. Smith, Ph.D.; Laura Colangelo, M.S.; and Kiang Liu, Ph.D.

Media advisory: Dr. Juo can be reached by telephone at 212-304-7320; by fax at 212-304-5515; and by e-mail at [email protected]. (Please do not publish these numbers.)

NR00-1138 (Circ/Juo)