IngentaConnect Estrogen receptor and APOE4 polymorphisms interact to increase ri...

Authors: Porrello, E.¹; Monti, M. C.²; Sinforiani, E.³; Cairati, M.⁴; Guaita, A.⁴; Montomoli, C.⁴; Govoni, S.¹; Racchi, M.¹

Source: European Journal of Neurology, Volume 13, Number 6, June 2006 , pp. 639-644(6)

Publisher: Blackwell Publishing

Abstract:

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects both sexes, with a higher prevalence in women. Declining estrogen levels after menopause may render estrogen target neurons in the brain more susceptible to age or disease-related processes such as AD. To investigate the role of two single nucleotide polymorphisms in the first intron of the ER-α gene, denominated PvuII and XbaI, and their interaction with the known AD susceptibility gene APOE, we examined 131 patients with sporadic AD and 109 healthy control subjects. In multinomial logistic regression analysis, a significantly increased risk of sporadic AD because of interaction between the ER-α p allele and APOE ɛ4 allele was observed in women, taking subjects who had neither the p allele nor ɛ4 as reference [odds ratio (OR) 7.24; 95% CI, 2.22–23.60]. For women carrying the ER-α x allele together with APOE ɛ4, the risk of sporadic AD was similarly elevated (OR 8.33; 95% CI, 1.73–40.06). The data suggest that the p and x alleles of polymorphic ER-α gene interact synergistically with the APOE ɛ4 allele to increase the risk of AD in women but not in men in this Italian cohort.

Keywords: Alzheimer's disease; apolipoprotein E; estrogen receptor; polymorphism; risk factor

Document Type: Research article

DOI: 10.1111/j.1468-1331.2006.01333.x

Affiliations: 1: Department of Experimental and Applied Pharmacology 2: Department of Health Sciences, Section of Medical Statistics and Epidemiology, University of Pavia 3: Alzheimer's Centre, Laboratory of Neuropsychology, IRCCS C. Mondino Institute of Neurology 4: Geriatric Institute `Camillo Golgi', Abbiategrasso (MI), Pavia, Italy

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Estrogen receptor α and APOEɛ4 polymorphisms interact to increase risk for sporadic AD in Italian females