a1 Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
a2 Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
a3 Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
a4 Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, P.R. China
a5 Joint Laboratory of Bioresources and Molecular Research in Common Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Background: Alzheimer's disease (AD) is a neurodegenerative disease with a higher prevalence in women. Expression of estrogen receptor 1 (ESR1) gene has been identified throughout the brain. Owing to the putative neuroprotective effects of estrogen, estrogen receptor gene is a potential candidate modulating the development of AD. Preliminary associations between two polymorphisms of ESR1 (PvuII and XbaI) gene and AD have been reported.
Methods: In this study, 16 single nucleotide polymorphisms (SNPs) of the ESR1 gene (including four commonly studied ESR1 SNPs and 12 other tagging SNPs selected from the HapMap database) were investigated to further evaluate the association between ESR1 polymorphisms and the risk of AD in the Chinese population.
Results: A total of 233 Chinese AD patients and 245 age-matched elderly control subjects were recruited. Genetic associations were analyzed by chi-square test and interaction effect was analysed by logistic regression analysis. Five SNPs (clustered between intron 3 and intron 7) were associated with the risk of AD (p-value ranges from 0.001 to 0.035); another two SNPs (located on exon 2 and intron 2) were shown to modulate the age-at-onset (AAO) in AD (p-value = 0.036 and 0.011).
Conclusions: ESR1 gene polymorphisms may be associated with the AAO in AD. The present results provided information for possible associations between certain polymorphisms of ESR1 gene and the risk of AD.
(Received November 20 2008)
(Revised February 03 2009)
(Revised April 07 2009)
(Accepted April 09 2009)
(Online publication July 09 2009)
c1 Correspondence should be addressed to: Linda C W Lam, Department of Psychiatry, The Chinese University of Hong Kong, Shatin, Hong Kong, China. Phone: +852-26076040; Fax: +852-26671255. Email: email@example.com.