Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease.
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.
Bretsky
P M
PM
Andrus Gerontology Center, University of Southern California, Los Angeles, USA.
Buckwalter
J G
JG
Seeman
T E
TE
Miller
C A
CA
Poirier
J
J
Schellenberg
G D
GD
Finch
C E
CE
Henderson
V W
VW
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
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005819:Genetic Markers