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

Department of Neurology, Boston University School of Medicine, Mass 02118, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/1997; 278(16):1349-56.
Source: PubMed


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.

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Available from: Lindsay Farrer, Jul 30, 2014
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    • "The ApoE protein, which is the product of the ApoE gene, is the carrier protein for cholesterol transport in the brain. The ApoE E4 allele is a widely accepted risk factor [22] [23] [24] [25] for AD. ApoE E3 is the most common allele in every human population studied to date [26]. "
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    • "Not all of the risk factors, however, depend entirely on chosen or imposed life styles but are, to a significant extent, determined by individual's genetic makeup[12]. For example, it is widely accepted that the presence of the ApoE4 allele of Apolipoprotein E gene greatly increases the probability of developing AD131415. Several other candidate gene polymorphisms have been associated with an increased risk of AD, too, though none of them as strongly as the presence of ApoE4 allele[12,16]. "
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    • "Risk factors present in humans may not be adequately modeled in rodents. For example, while variants in the APOE gene are the strongest genetic risk factors for sporadic AD identified to date (Bertram, et al., 2008; Corder, et al., 1993; Farrer, et al., 1997), the rodent genome has only one version of this gene. "
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