title: Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease.
abstract: Carriers of the apolipoprotein E (APOE) epsilon4 allele show significantly higher risk of Alzheimer disease (AD). The aim of this present study was to test the hypothesis that a significant interaction exists between APOE genotype and gender on AD. Interactions of epsilon4 by gender, although indicated in the literature, require further verification. A total of 195 past or current control or AD participants in an ongoing longitudinal study of aging and dementia were genotyped. All subjects were at least 60 years old; demented subjects met clinical or pathologic criteria for late-onset AD. Logistic regression analysis and proportional hazard models were used to evaluate joint effects of APOE and gender. A significant statistical interaction between APOE and gender was shown (p = 0.04) in logistic regression analysis. Women carrying one or more APOE-epsilon4 allele were more likely to develop AD [odds ratio (OR) = 7.8, 95% confidence interval (CI) = 3.2-19. 1]. For men, the presence of the APOE-epsilon4 allele was not associated with a statistically significant increased risk (OR = 1.6, 95% CI = 0.5-5.3). The interaction term in the proportional hazards model neared (p = 0.07) statistical significance, and a similar but reduced gender effect was shown. The analysis suggests that the presence of one or more APOE-epsilon4 allele confers a substantially greater risk of AD to women than to men. These findings in part may account for reports of increased risk of AD faced by women.
authors.affiliation: Andrus Gerontology Center, University of Southern California, Los Angeles, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Bretsky
authors.forename: J G
authors.initials: JG
authors.lastname: Buckwalter
authors.forename: T E
authors.initials: TE
authors.lastname: Seeman
authors.forename: C A
authors.initials: CA
authors.lastname: Miller
authors.forename: J
authors.initials: J
authors.lastname: Poirier
authors.forename: G D
authors.initials: GD
authors.lastname: Schellenberg
authors.forename: C E
authors.initials: CE
authors.lastname: Finch
authors.forename: V W
authors.initials: VW
authors.lastname: Henderson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005819:Genetic Markers