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Association Between Apolipoprotein E Genotype and Alzheimer Disease in African American Subjects
Neill R. Graff-Radford, MD;
Robert C. Green, MD, MPH;
Rodney C. P. Go, PhD;
Michael L. Hutton, PhD;
Timi Edeki, MD, PhD;
David Bachman, MD;
Jennifer L. Adamson, PhD;
Patrick Griffith, MD;
Floyd B. Willis, MD;
Mary Williams, EdD, PAC;
Yvonne Hipps, PhD;
Jonathan L. Haines, PhD;
L. Adrienne Cupples, PhD;
Lindsay A. Farrer, PhD
Arch Neurol. 2002;59:594-600.
Background The association between Alzheimer disease (AD) and genotypes at the
apolipoprotein E (APOE) locus has been confirmed
in numerous populations worldwide, but appears to be inconsistent in African
American subjects.
Objective To investigate the association between APOE
genotypes and AD in elderly African American subjects.
Design Clinic-based, multicenter case-control study and a family study.
Participants A total of 338 African American probands meeting criteria for probable
or definite AD, 301 cognitively healthy, elderly unrelated control subjects
(spouses and community volunteers), and 108 siblings of 88 AD probands.
Main Outcome Measures Odds of AD according to APOE genotype.
Results Compared with individuals with the APOE
 3/3, the odds of having AD were significantly increased
among those with 1 or more copies of the
4
allele; the odds ratio (OR) for the
3/4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the
OR for the 4/4 genotype
was 10.5 (95% CI, 5.1-21.8). These risks decreased substantially after 68
years of age. The risk for AD was lower among individuals with the
2/3 genotype (OR, 0.41; 95% CI, 0.22-0.79).
The patterns of association were similar in men and women. These results obtained
from comparisons of unrelated AD patients and controls were bolstered by results
of analysis of family data that showed preferential transmission of the
4 allele to demented siblings
(P<<.001)
and of the 2 allele to nondemented siblings
(P = .005).
Conclusions The presence of 1 or 2
4 alleles is a
determinant of AD risk in African American subjects. The age-related risk
for decline associated with the 4 allele and
the apparent protective effect of the 2 allele
are similar to patterns observed in white subjects.
From the Departments of Neurology (Dr Graff-Radford), Neuroscience
(Drs Hutton and Adamson), and Family Practice (Dr Willis), Mayo Clinic, Jacksonville,
Fla; the Genetics Program, Department of Medicine, and the Department of Neurology,
Boston University School of Medicine (Drs Green and Farrer), and the Department
of Epidemiology and Biostatistics, Boston University School of Public Health
(Drs Cupples and Farrer), Boston, Mass; the Department of Epidemiology, University
of Alabama, Birmingham (Dr Go); the Departments of Pharmacology (Dr Edeki)
and Medicine (Drs Edeki, Griffith, Williams, and Hipps), Morehouse School
of Medicine, Atlanta, Ga; the Department of Neurology, Medical University
of South Carolina, Charleston (Dr Bachman); and the Program in Human Genetics,
Vanderbilt University School of Medicine, Nashville, Tenn (Dr Haines).
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