Altered Gene Protects Some African-Americans From Heart Disease

Jan 31, 2011

A study by scientists at Johns Hopkins discovered that a single alteration in the genetic code in about a fourth of African-Americans helps protect them from coronary artery disease, the leading cause of death in Americans of all races.

The research shows that otherwise healthy African-American men and women with an alternative genetic code have a fivefold reduction in the likelihood that their arteries would narrow or clog.

For African-Americans who inherited two copies of the guanine gene variant, one from each parent, the risk reduction was even more dramatic. They were 10 times less likely to have coronary heart disease, which disproportionately afflicts a greater number of African-Americans than whites or any other ethnic group.

Nearly 17 million Americans have an arterial problem plaguing the heart, causing a half-million deaths, annually.

“What we think we have here is the first confirmed hereditary link to cardiovascular disease among African-Americans and it is a protective one,” says senior study investigator and health epidemiologist Diane Becker, M.P.H., Sc.D. “This newly found link in African-Americans was not only protective instead of harmful but was also found at a precise location on gene CDKN2B, a gene close to the single base pair modification tied to other increased risk of coronary artery disease in other races.”

Becker emphasizes that only an estimated quarter of blacks have the protective CDKN2B code, and only 6 percent have two copies, so “while a lot of African-Americans have this protective genetic modification, most do not.” Advance testing for the genetic marker, she says, could ultimately in the future assist physicians in risk-stratifying those without inherited protection so they could be monitored more closely for early signs and symptoms of disease.

The findings appeared in the Journal of Human Genetics online Jan. 27.

Becker, a professor at both the Johns Hopkins University School of Medicine and Hopkins’ Bloomberg School of Public Health, and a team that included researchers at Duke and Emory universities, also say their results, based on blood analysis from 548 black men and women in the Baltimore region and confirmed in several hundred more in the Atlanta and Durham, N.C., regions, help explain why earlier studies found potentially dangerous genetic connections to this type of heart disease in Caucasians, Hispanics and Asians, but failed to find a negative tie-in to the disease in blacks.

Earlier studies, says Becker, had involved genome-wide reviews in multiracial populations and taken “a needle in the haystack approach” to finding that one change in a string of some 58,000 base pairs, in a chromosomal region known as 9p21. That region, which includes CDKN2B, is associated with higher rates of coronary disease in non-blacks.

The team’s latest analysis was successful, she believes, because it had a large and sufficiently broadly based black volunteer population. The study group comprised men and women between the ages of 26 and 60. Investigators also focused on the 9p21 region and a subsection of genetic material within called ANRIL that overlaps and is closely held to CDKN2B, but away from the deleterious genetic variant found earlier.

Johns Hopkins cardiologist Brian Kral, M.D., M.P.H., says the abundance of activity in this particular region of the genome, including CDK2NB and ANRIL, suggests that everyday replication of this zone could play a more fundamental, underlying role in the progression of coronary artery disease in all races.

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