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ORLANDO, Feb. 6 -- Genetic variations in apolipoprotein E, a key protein involved in the transport and disposal of cholesterol in the body, may be associated in African Americans with the occurrence of a stroke caused by bleeding in the brain.
In a presentation today at the American Heart Association's 23rd Joint International Conference on Stroke and Cerebral Circulation, researchers from Duke University said an increase in the variation of a certain gene known as the e4 allele has been shown to be a possible determinant of the potential for these strokes, called intracerebral hemorrhage (ICH).
"This finding is important because it may help us understand why African Americans suffer more from intracerebral hemorrhage and why they get it at a younger age than Caucasians," says Mark Alberts, M.D., associate professor of medicine, division of neurology and director, Stroke Acute Care Unit at Duke University.
The culprit variant, e4, is one of three known alternative forms, or alleles, of the gene encoding for apo E. Located on the surface of circulating blood-fat particles, apo E normally binds to liver cells, helping them to clear cholesterol from the blood. When genetically defective apo E fails to do its job, higher levels of "bad" LDL cholesterol result, setting the stage for atherosclerosis, the disease process that can create the blood vessel obstruction that can trigger a heart attack or stroke.
"We and others have observed that African Americans tend to be more likely to have bleeding strokes and have a worse outcome," says Alberts. "We believe the e4 allele is a predictor of a poorer outcome after stroke and may be associated with more severe stroke."
In one of the largest such studies undertaken to date, the researchers examined 124 patients -- 63 males and 61 females between the ages of 30 and 88 -- who had suffered ICH. Eighty-one percent of patients were Caucasian and 18 percent were African American. The scientists found an increase in the e4 allele and the presence of two copies of e4, one from each parent, among
African-American patients compared to Caucasians with an ICH. In comparison with a reference population of 1,899 people, there was a significant increase in the e4 allele frequency and the e4/e4 genotype frequency between the ICH patients and the reference population. In the study, ICH was found to occur at a younger age in African Americans (mean age of 56.7 years) compared to Caucasians (mean age 64.3 years).
The e4 allele frequency was 28 percent in the study's African-American ICH patients and 14 percent in the reference population. The e4/e4 genotype frequency was 17 percent in the African-American patients compared to 2 percent in the reference population.
The increase in the e4 allele frequency in African-American patients who have had a bleeding stroke may explain the increased occurrence and severity of this form of stroke among some African Americans.
"These results feed into our concept that this e4 allele doesn't only lead to worse outcomes, but it also may also lead to an earlier onset," says Alberts.
Co-researchers include S.E. Moore, B.A.; K.L Hoffman, R.N; D.M. Delong, Ph.D.; C. Graffagnino, M.D.; C. Granger, M.D. and A.M. Saunders, Ph.D. of Duke University Medical Center, Durham, N.C.
Media advisory: Dr. Alberts can be reached at (919) 684-5650. (Please do not publish telephone numbers.)