Association between apolipoprotein E genotype and Alzheimer disease in African American subjects

被引:80
作者
Graff-Radford, NR
Green, RC
Go, RCP
Hutton, ML
Edeki, T
Bachman, D
Adamson, JL
Griffith, P
Willis, FB
Williams, M
Hipps, Y
Haines, JL
Cupples, LA
Farrer, LA
机构
[1] Boston Univ, Sch Med, Genet Program L320, Dept Med, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
[3] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA
[4] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA
[5] Mayo Clin, Dept Family Practice, Jacksonville, FL 32224 USA
[6] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA
[7] Univ Alabama, Dept Epidemiol, Birmingham, AL USA
[8] Morehouse Sch Med, Dept Pharmacol, Atlanta, GA 30310 USA
[9] Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA
[10] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA
[11] Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA
关键词
D O I
10.1001/archneur.59.4.594
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 epsilon3/epsilon3 genotype, the odds of having AD were significantly increased among those with 1 or more copies of the epsilon4 allele; the odds ratio (OR) for the epsilon3/epsilon4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the OR for the epsilon4/epsilon4 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 epsilon2/epsilon3 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 epsilon4 allele to demented siblings (P<<.001) and of the epsilon2 allele to nondemented siblings (P=.005). Conclusions: The presence of 1 or 2 epsilon4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the epsilon4 allele and the apparent protective effect of the epsilon2 allele are similar to patterns observed in white subjects.
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页码:594 / 600
页数:7
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