Public Release: 

Study Finds Gene Is Associated With Higher Risk Of One Kind of Stroke Among African-Americans

Duke University Medical Center

ORLANDO, Fla. -- The variant form of a gene that has been implicated in the most common form of Alzheimer's disease also may predispose blacks to intracerebral hemorrhages (ICH), a severe form of stroke, researchers from Duke University Medical Center reported Friday.

The researchers also found that overall, these strokes occurred in African Americans at a much earlier age -- on average, more than seven years earlier.

Duke neurologist Dr. Mark J. Alberts prepared the results of the study for presentation Friday at the American Heart Association's 23rd International Joint Conference on Cerebral Circulation and Stroke.

The gene, located on chromosome 19, is the blueprint for the production of apolipoprotein-E (apo-E), a protein that is responsible for transport and disposal of cholesterol within the central nervous system. The researchers focused on one of the gene's three known variants, or alleles -- the one called e4.

They found that in the study, blacks with a single e4 allele, inherited from one parent, were twice as likely to have ICH when compared to control groups; they were more than eight times as likely to have these strokes if they had two alleles (one from each parent).

"Past studies have shown that African Americans tend to have a higher occurrence of ICH than Caucasians, and that they tend to die at a higher rate," Alberts said. While not nearly as common as strokes caused by blockages in vessels in the brain (85 percent of all strokes), ICHs are much more severe, with a mortality rate approaching 50 percent, Alberts said.

"This study demonstrates that the e4 allele may be a strong predictor of which African Americans are most likely to suffer from intracerebral bleeds," Alberts said.

The Duke team conducted genetic analysis on 124 patients (63 males and 61 females between the ages of 30 and 88) who suffered from ICH due to hypertension, amyloid angiopathy (blockages in small brain vessels) or as a result of clot-busting therapy for a heart attack. Eighty-one percent were white and 19 percent were black.

In comparison to a control group of 1,899 people, there was a statistically significant increase in the e4 and the double e4 frequencies between the ICH patients and the control group, due largely to the increased frequency of e4 in the black patients.

"In our study group, 28 percent of the African Americans had one e4 allele, compared to 14 percent for Caucasians," Alberts said. "Furthermore, 17 percent of the African Americans had two e4 alleles, and only 2 percent of whites did."

"Interestingly, the increase in the number of e4 alleles is not explainable by the presence of Alzheimer's disease, since only two African Americans had evidence of probable Alzheimer's," he said.

The average age for black ICH patients was 56.7 years; for whites it was 64.3.

"These findings will help us gain a better understanding of ICH," Alberts said. "We know that the most common risk factor for ICH is hypertension. But there must be other factors involved, since more than 40 million Americans have high blood pressure, yet most do not develop intracerebral bleeds.

"Having the e4 allele in one's genetic makeup just might be one of those additional risk factors if you are an African American," Alberts continued.

Apo-E, which is located on the surface of circulating blood-fat particles, normally binds to liver cells, helping them clear cholesterol from the blood. The Apo-E4 variant is unable to function properly, leading to a build-up of "bad" LDL cholesterol, which in turn can lead to atherosclerosis, a disease process that can create plaque in blood vessels that can lead to a heart attack or stroke.

Duke neurologists and genetic researchers presented a novel view of Alzheimer's disease when they demonstrated, in 1993, that the Apo-E4 variant was a risk factor predisposing people to developing the disease. Those with the e4 variant tended to get the disease at an earlier age. Since that time, these researchers, some of whom participated in the current ICH study, have since changed the focus of Alzheimer's disease research to genetic risk factors.

Joining Alberts in the study, from Duke, were Sara Elizabeth Moore, Kathleen Hoffman, David DeLong, Ph.D., Dr. Carmelo Graffagnino; Dr. Christopher Granger; and Ann Saunders, Ph.D.

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