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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
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1997
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Neurodegenerative DiseasesApolipoprotein E GenotypeAlzheimer's DiseaseAgingApolipoprotein EApoe GenotypeDementiaMedicineGenetic EpidemiologyVascular DementiaNeurologyAlzheimer DiseaseAging-associated DiseasePublic HealthEpidemiology Of AgingRisk FactorsEpidemiology
The association between APOE ε4 and Alzheimer’s disease in African Americans is unclear, and its reduced effect in Hispanics warrants further study. The study aimed to evaluate how APOE genotype, age, and sex influence Alzheimer’s disease risk across diverse ethnic populations. Data from 40 studies comprising 5,930 AD patients and 8,607 controls were pooled, and logistic regression was used to compute ethnicity‑specific odds ratios for each APOE genotype, adjusting for age and study source. Epsilon4 markedly increased AD risk in Caucasians and Japanese but was weaker in African Americans and Hispanics; epsilon2/epsilon3 was protective across groups, and the epsilon4 effect persisted from ages 40 to 90, declining after 70 and differing by sex, confirming ε4 as a major risk factor in all studied populations.
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.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.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.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.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.