Interaction between estrogen receptor 1 and the ε4 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 expression may be modified by DNA polymorphisms. Here the estrogen receptor 1 gene (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 the apolipoprotein E epsilon 4 allele was observed in women in a Swedish clinic-based sample, taking subjects who had neither the xx genotype nor epsilon 4 as reference (OR 11.3, 95% CI 2.9-43.8). The risk of AD was more pronounced 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 together with epsilon 4 the risk of AD was similarly elevated. Likewise in a Swedish community-based set of women, an increased risk of familial AD was observed in subjects who had either the ESR1 xx or pp genotype together with epsilon 4. Furthermore, the Pp genotype frequency was found to be significantly increased in Finnish women with sporadic AD. We, thus, conclude that the ESR1 gene may have a role in the development of AD in females. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.