Interaction between estrogen receptor 1 and the epsilon 4 allele of apolipoprotein E increases the risk of familial Alzheimer's disease in women

Estrogens may be implicated in the development of Alzheimer's disease (AD). Most of their effects are mediated via receptors whose function and expres sion may be modified by DNA polymorphisms. Here the estrogen receptor 1 gen e (ESR?) polymorphisms Xbal and Pvull were analyzed 1 in 214 AD patients a nd 290 controls. in logistic regression analysis, a significantly increased risk of familiar AD due to interaction between the ESR1 xx genotype and th e apolipoprotein E epsilon 4 allele was observed in women in a Swedish clin ic-based sample, taking subjects who had neither the xx genotype nor epsilo n 4 as reference (OR 11.3, 95% CI 2.9-43.8). The risk of AD was more pronou nced in early-onset (OR 22.0, 95% CI 3.7-132.7) than in late-onset (OR 6.0, 95% CI 1.2-29.7) female patients. For women carrying the pp genotype toget her with epsilon 4 the risk of AD was similarly elevated. Likewise in a Swe dish community-based set of women, an increased risk of familial AD was obs erved in subjects who had either the ESR1 xx or pp genotype together with e psilon 4. Furthermore, the Pp genotype frequency was found to be significan tly increased in Finnish women with sporadic AD. We, thus, conclude that th e ESR1 gene may have a role in the development of AD in females. (C) 2000 E lsevier Science Ireland Ltd. All rights reserved.