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Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium.
JAMA. 1997 Oct 22-29; 278(16):1349-56.JAMA

Abstract

OBJECTIVE

To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations.

DATA SOURCES

Forty research teams contributed data on APOE genotype, sex, age at disease onset, and ethnic background for 5930 patients who met criteria for probable or definite AD and 8607 controls without dementia who were recruited from clinical, community, and brain bank sources.

MAIN OUTCOME MEASURES

Odds ratios (ORs) and 95% confidence intervals (CIs) for AD, adjusted for age and study and stratified by major ethnic group (Caucasian, African American, Hispanic, and Japanese) and source, were computed for APOE genotypes epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon4, and epsilon4/epsilon4 relative to the epsilon3/epsilon3 group. The influence of age and sex on the OR for each genotype was assessed using logistic regression procedures.

RESULTS

Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes epsilon2/epsilon4 (OR=2.6, 95% CI=1.6-4.0), epsilon3/epsilon4 (OR=3.2, 95% CI=2.8-3.8), and epsilon4/epsilon4 (OR=14.9, 95% CI= 10.8-20.6); whereas, the ORs were decreased for people with genotypes epsilon2/epsilon2 (OR=0.6, 95% CI=0.2-2.0) and epsilon2/epsilon3 (OR=0.6, 95% CI=0.5-0.8). The APOE epsilon4-AD association was weaker among African Americans and Hispanics, but there was significant heterogeneity in ORs among studies of African Americans (P<.03). The APOE epsilon4-AD association in Japanese subjects was stronger than in Caucasian subjects (epsilon3/epsilon4: OR=5.6, 95% CI=3.9-8.0; epsilon4/epsilon4: OR=33.1, 95% CI=13.6-80.5). The epsilon2/epsilon3 genotype appears equally protective across ethnic groups. We also found that among Caucasians, APOE genotype distributions are similar in groups of patients with AD whose diagnoses were determined clinically or by autopsy. In addition, we found that the APOE epsilon4 effect is evident at all ages between 40 and 90 years but diminishes after age 70 years and that the risk of AD associated with a given genotype varies with sex.

CONCLUSIONS

The APOE epsilon4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women. The association between APOE epsilon4 and AD in African Americans requires clarification, and the attenuated effect of APOE epsilon4 in Hispanics should be investigated further.

Links

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Authors+Show Affiliations

Farrer LA
Department of Neurology, Boston University School of Medicine, Mass 02118, USA. farrer@neugen.bu.edu
Cupples LA
No affiliation info available
Haines JL
No affiliation info available
Hyman B
No affiliation info available
Kukull WA
No affiliation info available
Mayeux R
No affiliation info available
Myers RH
No affiliation info available
Pericak-Vance MA
No affiliation info available
Risch N
No affiliation info available
van Duijn CM
No affiliation info available

MeSH

AdultAge FactorsAgedAged, 80 and overAllelesAlzheimer DiseaseApolipoproteins EAsiansBlacksFemaleGenotypeHispanic or LatinoHumansLogistic ModelsMaleMiddle AgedRacial GroupsRisk FactorsWhites

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9343467

Clinical Trial Links

Risk Evaluation and Education for Alzheimer's Disease
Longitudinal Early-onset Alzheimer's Disease Study Protocol

Citation

Farrer, L A., et al. "Effects of Age, Sex, and Ethnicity On the Association Between Apolipoprotein E Genotype and Alzheimer Disease. a Meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium." JAMA, vol. 278, no. 16, 1997, pp. 1349-56.
Farrer LA, Cupples LA, Haines JL, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278(16):1349-56.
Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R., Myers, R. H., Pericak-Vance, M. A., Risch, N., & van Duijn, C. M. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA, 278(16), 1349-56.
Farrer LA, et al. Effects of Age, Sex, and Ethnicity On the Association Between Apolipoprotein E Genotype and Alzheimer Disease. a Meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997 Oct 22-29;278(16):1349-56. PubMed PMID: 9343467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. AU - Farrer,L A, AU - Cupples,L A, AU - Haines,J L, AU - Hyman,B, AU - Kukull,W A, AU - Mayeux,R, AU - Myers,R H, AU - Pericak-Vance,M A, AU - Risch,N, AU - van Duijn,C M, PY - 1997/10/29/pubmed PY - 1997/10/29/medline PY - 1997/10/29/entrez SP - 1349 EP - 56 JF - JAMA JO - JAMA VL - 278 IS - 16 N2 - OBJECTIVE: To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations. DATA SOURCES: Forty research teams contributed data on APOE genotype, sex, age at disease onset, and ethnic background for 5930 patients who met criteria for probable or definite AD and 8607 controls without dementia who were recruited from clinical, community, and brain bank sources. MAIN OUTCOME MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for AD, adjusted for age and study and stratified by major ethnic group (Caucasian, African American, Hispanic, and Japanese) and source, were computed for APOE genotypes epsilon2/epsilon2, epsilon2/epsilon3, epsilon2/epsilon4, epsilon3/epsilon4, and epsilon4/epsilon4 relative to the epsilon3/epsilon3 group. The influence of age and sex on the OR for each genotype was assessed using logistic regression procedures. RESULTS: Among Caucasian subjects from clinic- or autopsy-based studies, the risk of AD was significantly increased for people with genotypes epsilon2/epsilon4 (OR=2.6, 95% CI=1.6-4.0), epsilon3/epsilon4 (OR=3.2, 95% CI=2.8-3.8), and epsilon4/epsilon4 (OR=14.9, 95% CI= 10.8-20.6); whereas, the ORs were decreased for people with genotypes epsilon2/epsilon2 (OR=0.6, 95% CI=0.2-2.0) and epsilon2/epsilon3 (OR=0.6, 95% CI=0.5-0.8). The APOE epsilon4-AD association was weaker among African Americans and Hispanics, but there was significant heterogeneity in ORs among studies of African Americans (P<.03). The APOE epsilon4-AD association in Japanese subjects was stronger than in Caucasian subjects (epsilon3/epsilon4: OR=5.6, 95% CI=3.9-8.0; epsilon4/epsilon4: OR=33.1, 95% CI=13.6-80.5). The epsilon2/epsilon3 genotype appears equally protective across ethnic groups. We also found that among Caucasians, APOE genotype distributions are similar in groups of patients with AD whose diagnoses were determined clinically or by autopsy. In addition, we found that the APOE epsilon4 effect is evident at all ages between 40 and 90 years but diminishes after age 70 years and that the risk of AD associated with a given genotype varies with sex. CONCLUSIONS: The APOE epsilon4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women. The association between APOE epsilon4 and AD in African Americans requires clarification, and the attenuated effect of APOE epsilon4 in Hispanics should be investigated further. SN - 0098-7484 UR - https://www.unboundmedicine.com/medline/citation/9343467/Effects_of_age_sex_and_ethnicity_on_the_association_between_apolipoprotein_E_genotype_and_Alzheimer_disease__A_meta_analysis__APOE_and_Alzheimer_Disease_Meta_Analysis_Consortium_ L2 - https://jamanetwork.com/journals/jama/fullarticle/vol/278/pg/1349 DB - PRIME DP - Unbound Medicine ER -