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

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

Research output: Contribution to journalArticle

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Abstract

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 ε3/ε3 genotype, the odds of having AD were significantly increased among those with 1 or more copies of the ε4 allele; the odds ratio (OR) for the ε3/ε4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the OR for the ε4/ε4 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 ε2/ε3 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 ε4 allele to demented siblings (P<<.001) and of the ε2 allele to nondemented siblings (P=.005). Conclusions: The presence of 1 or 2 ε4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the ε4 allele and the apparent protective effect of the ε2 allele are similar to patterns observed in white subjects.

Original languageEnglish (US)
Pages (from-to)594-600
Number of pages7
JournalArchives of Neurology
Volume59
Issue number4
StatePublished - 2002

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Apolipoproteins E
African Americans
Alzheimer Disease
Genotype
Alleles
Siblings
Odds Ratio
Confidence Intervals
Apolipoprotein E3
Alzheimer's Disease
Spouses
Allele
Case-Control Studies
Volunteers
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Graff Radford, N. R., Green, R. C., Go, R. C. P., Hutton, M. L., Edeki, T., Bachman, D., ... Farrer, L. A. (2002). Association between apolipoprotein E genotype and Alzheimer disease in African American subjects. Archives of Neurology, 59(4), 594-600.

Association between apolipoprotein E genotype and Alzheimer disease in African American subjects. / Graff Radford, Neill R; Green, Robert C.; Go, Rodney C P; Hutton, Michael L.; Edeki, Timi; Bachman, David; Adamson, Jennifer L.; Griffith, Patrick; Willis, Floyd Banard; Williams, Mary; Hipps, Yvonne; Haines, Jonathan L.; Adrienne Cupples, L.; Farrer, Lindsay A.

In: Archives of Neurology, Vol. 59, No. 4, 2002, p. 594-600.

Research output: Contribution to journalArticle

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, Adrienne Cupples, L & Farrer, LA 2002, 'Association between apolipoprotein E genotype and Alzheimer disease in African American subjects', Archives of Neurology, vol. 59, no. 4, pp. 594-600.
Graff Radford, Neill R ; Green, Robert C. ; Go, Rodney C P ; Hutton, Michael L. ; Edeki, Timi ; Bachman, David ; Adamson, Jennifer L. ; Griffith, Patrick ; Willis, Floyd Banard ; Williams, Mary ; Hipps, Yvonne ; Haines, Jonathan L. ; Adrienne Cupples, L. ; Farrer, Lindsay A. / Association between apolipoprotein E genotype and Alzheimer disease in African American subjects. In: Archives of Neurology. 2002 ; Vol. 59, No. 4. pp. 594-600.
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abstract = "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 ε3/ε3 genotype, the odds of having AD were significantly increased among those with 1 or more copies of the ε4 allele; the odds ratio (OR) for the ε3/ε4 genotype was 2.6 (95{\%} confidence interval [CI], 1.8-3.7), and the OR for the ε4/ε4 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 ε2/ε3 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 ε4 allele to demented siblings (P<<.001) and of the ε2 allele to nondemented siblings (P=.005). Conclusions: The presence of 1 or 2 ε4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the ε4 allele and the apparent protective effect of the ε2 allele are similar to patterns observed in white subjects.",
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T1 - Association between apolipoprotein E genotype and Alzheimer disease in African American subjects

AU - Graff Radford, Neill R

AU - Green, Robert C.

AU - Go, Rodney C P

AU - Hutton, Michael L.

AU - Edeki, Timi

AU - Bachman, David

AU - Adamson, Jennifer L.

AU - Griffith, Patrick

AU - Willis, Floyd Banard

AU - Williams, Mary

AU - Hipps, Yvonne

AU - Haines, Jonathan L.

AU - Adrienne Cupples, L.

AU - Farrer, Lindsay A.

PY - 2002

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N2 - 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 ε3/ε3 genotype, the odds of having AD were significantly increased among those with 1 or more copies of the ε4 allele; the odds ratio (OR) for the ε3/ε4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the OR for the ε4/ε4 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 ε2/ε3 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 ε4 allele to demented siblings (P<<.001) and of the ε2 allele to nondemented siblings (P=.005). Conclusions: The presence of 1 or 2 ε4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the ε4 allele and the apparent protective effect of the ε2 allele are similar to patterns observed in white subjects.

AB - 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 ε3/ε3 genotype, the odds of having AD were significantly increased among those with 1 or more copies of the ε4 allele; the odds ratio (OR) for the ε3/ε4 genotype was 2.6 (95% confidence interval [CI], 1.8-3.7), and the OR for the ε4/ε4 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 ε2/ε3 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 ε4 allele to demented siblings (P<<.001) and of the ε2 allele to nondemented siblings (P=.005). Conclusions: The presence of 1 or 2 ε4 alleles is a determinant of AD risk in African American subjects. The age-related risk for decline associated with the ε4 allele and the apparent protective effect of the ε2 allele are similar to patterns observed in white subjects.

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