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

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 APOEepsilon3/epsilon3, 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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  • Authors+Show Affiliations

    ,

    Genetics Program L-320, Boston University School of Medicine, 715 Albany St, Boston, MA 02118, USA. farrer@neugen.bu.edu

    , , , , , , , , , , , ,

    Source

    Archives of neurology 59:4 2002 Apr pg 594-600

    MeSH

    African Americans
    African Continental Ancestry Group
    Age Distribution
    Aged
    Aged, 80 and over
    Alleles
    Alzheimer Disease
    Apolipoproteins E
    Case-Control Studies
    Female
    Genotype
    Humans
    Male
    Odds Ratio
    United States

    Pub Type(s)

    Journal Article
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    11939894

    Citation

    Graff-Radford, Neill R., et al. "Association Between Apolipoprotein E Genotype and Alzheimer Disease in African American Subjects." Archives of Neurology, vol. 59, no. 4, 2002, pp. 594-600.
    Graff-Radford NR, Green RC, Go RC, et al. Association between apolipoprotein E genotype and Alzheimer disease in African American subjects. Arch Neurol. 2002;59(4):594-600.
    Graff-Radford, N. R., Green, R. C., Go, R. C., 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), pp. 594-600.
    Graff-Radford NR, et al. Association Between Apolipoprotein E Genotype and Alzheimer Disease in African American Subjects. Arch Neurol. 2002;59(4):594-600. PubMed PMID: 11939894.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR 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 B, AU - Williams,Mary, AU - Hipps,Yvonne, AU - Haines,Jonathan L, AU - Cupples,L Adrienne, AU - Farrer,Lindsay A, PY - 2002/4/10/pubmed PY - 2002/4/20/medline PY - 2002/4/10/entrez SP - 594 EP - 600 JF - Archives of neurology JO - Arch. Neurol. VL - 59 IS - 4 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 APOEepsilon3/epsilon3, 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. SN - 0003-9942 UR - https://www.unboundmedicine.com/medline/citation/11939894/Association_between_apolipoprotein_E_genotype_and_Alzheimer_disease_in_African_American_subjects_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/vol/59/pg/594 DB - PRIME DP - Unbound Medicine ER -