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Association Between Apolipoprotein E Genotype and Alzheimer Disease in African American Subjects

2002; American Medical Association; Volume: 59; Issue: 4 Linguagem: Inglês

10.1001/archneur.59.4.594

1538-3687

Neill R. Graff‐Radford, Robert C. Green, Rodney C.P. Go, Michael Hutton, Timi Edeki, David Bachman, Jennifer Adamson, Patrick Griffith, Floyd B. Willis, Mary Williams, Yvonne G. Hipps, Jonathan L. Haines, L. Adrienne Cupples, Lindsay A. Farrer,

Nuclear Receptors and Signaling

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 ϵ 3 /ϵ 3 , the odds of having AD were significantly increased among those with 1 or more copies of the ϵ 4 allele; the odds ratio (OR) for the ϵ 3 /ϵ 4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the OR for the ϵ 4 /ϵ 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 ϵ 2 /ϵ 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 ϵ 4 allele to demented siblings ( P <<.001) and of the ϵ 2 allele to nondemented siblings ( P = .005). Conclusions The presence of 1 or 2 ϵ 4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the ϵ 4 allele and the apparent protective effect of the ϵ 2 allele are similar to patterns observed in white subjects.