September 25, 2016
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Gene Protects Blacks From Coronary Disease

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

Researchers found that a single DNA variation -- having at least one 
so-called guanine nucleotide in a base pair instead of a combination 
without any guanine -- on a gene already linked to higher risk of 
coronary disease in other races is linked in blacks to decreased 
risk. Specifically, the study showed that otherwise healthy 
African-American men and women with the alternative genetic code had 
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.

 Becker, a professor at both the Johns Hopkins University School of 
Medicine and the university's 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.

Kral, an assistant professor at Johns Hopkins and its Heart and 
Vascular Institute. was co-lead investigator of the latest study, 
along with Johns Hopkins genetic epidemiologist Rasika Mathias, Sc.D. 
The team next plans to further investigate the ANRIL subregion of 
9p21 to see if any single genetic changes speed up or slow down 
progression of coronary diseases.

Blood samples for the genetic analysis came from a larger study being 
led by Becker of some 4,000 people from white and African-American 
ethnic backgrounds. Called the Genetic Study of Atherosclerosis Risk 
(GeneSTAR), under way at Johns Hopkins since 1983, it involves 
participants who were all healthy upon enrollment, with no existing 
symptoms of heart disease. All were monitored for at least five 
years with periodic check-ups to see who developed heart disease and 
who did not. Each had a sibling or a parent who had a history of 
coronary artery disease or some other symptom of blocked arteries, 
such as chest pain or shortness of breath. The latest study was 
based on results collected through 2007, by which time 35 black study 
participants had suffered some form of heart attack or needed an 
angioplasty or X-ray scan of the heart's blood vessels to confirm or 
rule out arterial blockages.

Study funding was provided by the National Heart, Lung and Blood 
Institute (NHLBI), a member of the National Institutes of Health, and 
the Johns Hopkins Clinical Research Center.

In addition to Becker, Kral and Mathias, other Hopkins researchers 
involved in this report are Bhoom Suktitipar, M.D.; Ingo Ruczinski, 
Ph.D.; Dhananjay "Jay" Vaidya, M.B.B.S., Ph.D.; Lisa Yanek, M.P.H.; 
and Lewis Becker, M.D. Arshed Quyyumi, M.D.; Riyaz Patel, M.D.; A 
Maziar Zafari, M.D., Ph.D.; and Viola Vaccarino, M.D., Ph.D., all at 
Emory University in Atlanta, also contributed to the 
research. Further study assistance and support was provided from 
Elizabeth Hauser, Ph.D., and William Kraus, M.D., both at Duke 
University Medical Center in Durham, N.C.


STORY TAGS: BLACK NEWS, AFRICAN AMERICAN NEWS, MINORITY NEWS, CIVIL RIGHTS NEWS, DISCRIMINATION, RACISM, RACIAL EQUALITY, BIAS, EQUALITY, AFRO AMERICAN NEWS

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