Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-04T21:35:25.921Z Has data issue: false hasContentIssue false
  • English
  • Français

Polymorphisms of the estrogen receptor α (ESR1) gene and the risk of Alzheimer's disease in a southern Chinese community

Published online by Cambridge University Press:  09 July 2009

Suk L. Ma ,
Nelson L. S. Tang ,
Cindy W. C. Tam ,
Victor W. C. Lui ,
Edmond S. S. Lau ,
Ya P. Zhang ,
Helen F. K. Chiu  and
Linda C. W. Lam
Suk L. Ma
Affiliation:
Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Nelson L. S. Tang
Affiliation:
Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China Joint Laboratory of Bioresources and Molecular Research in Common Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Cindy W. C. Tam
Affiliation:
Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Victor W. C. Lui
Affiliation:
Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Edmond S. S. Lau
Affiliation:
Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Ya P. Zhang
Affiliation:
Laboratory of Cellular and Molecular Evolution, and Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, P.R. China Joint Laboratory of Bioresources and Molecular Research in Common Diseases, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Helen F. K. Chiu
Affiliation:
Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
Linda C. W. Lam*
Affiliation:
Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
*
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 protected].
Get access Rights & Permissions [Opens in a new window]

Abstract

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.

Keywords

Alzheimer's diseasepolymorphismestrogen receptorChinese
Type
Research Article
Information
International Psychogeriatrics , Volume 21 , Issue 5 , October 2009 , pp. 977 - 986
Copyright
Copyright © International Psychogeriatric Association 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anandappa, S. Y. et al. (2000). Variant estrogen receptor alpha mRNAs in human breast cancer specimens. International Journal of Cancer, 88, 209–216.Google Scholar
Badger, A. M. et al. (1999). Idoxifene, a novel selective estrogen receptor modulator, is effective in a rat model of adjuvant-induced arthritis. Journal of Pharmacology and Experimental Therapeutics, 291, 1380–1386.Google Scholar
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D. and Tanzi, R. E. (2007). Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database. Nature Genetics, 39, 17–23.CrossRefGoogle ScholarPubMed
Birge, S. J. (1997). The role of estrogen in the treatment of Alzheimer's disease. Neurology, 48, S36–41.CrossRefGoogle ScholarPubMed
Brandi, M. L. et al. (1999). Association of the estrogen receptor alpha gene polymorphisms with sporadic Alzheimer's disease. Biochemical and Biophysical Research Communications, 265, 335–338.Google Scholar
Cai, Q. et al. (2003). Genetic polymorphisms in the estrogen receptor alpha gene and risk of breast cancer: results from the Shanghai Breast Cancer Study. Cancer Epidemiology Biomarkers and Prevention, 12, 853–859.Google ScholarPubMed
Chiu, H. F. K., Lee, H. C., Chung, W. S. and Kwong, P. K. (1994). Reliability and validity of the Cantonese version of the Min-Mental State Examination – a preliminary study. Journal of the Hong Kong College of Psychiatrists, 4, 25–28.Google Scholar
Dijkstra, A. et al. (2006). Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma. Journal of Allergy and Clinical Immunology, 117, 604–611.CrossRefGoogle ScholarPubMed
Garcia Pedrero, J. M., Zuazua, P., Martinez-Campa, C., Lazo, P. S. and Ramos, S. (2003). The naturally occurring variant of estrogen receptor (ER) ERDeltaE7 suppresses estrogen-dependent transcriptional activation by both wild-type ERalpha and ERbeta. Endocrinology, 144, 2967–2976.CrossRefGoogle ScholarPubMed
Henderson, V. W., Benke, K. S., Green, R. C., Cupples, L. A. and Farrer, L. A. (2005). Postmenopausal hormone therapy and Alzheimer's disease risk: interaction with age. Journal of Neurology Neurosurgery and Psychiatry, 76, 103–105.CrossRefGoogle ScholarPubMed
International HapMap Consortium (2003). The International HapMap Project. Nature, 426, 789–796.CrossRefGoogle Scholar
Jaffe, A. B., Toran-Allerand, C. D., Greengard, P. and Gandy, S. E. (1994). Estrogen regulates metabolism of Alzheimer amyloid beta precursor protein. Journal of Biological Chemistry, 269, 13065–13068.CrossRefGoogle ScholarPubMed
Ji, Y., Urakami, K., Wada-Isoe, K., Adachi, Y. and Nakashima, K. (2000). Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia. Dementia and related Geriatrics Cognitive Disorders, 11, 119–122.CrossRefGoogle ScholarPubMed
Kang, H. J. et al. (2002). Polymorphisms in the estrogen receptor-alpha gene and breast cancer risk. Cancer Letters, 178, 175–180.CrossRefGoogle ScholarPubMed
Lambert, J. C. et al. (2001). Are the estrogen receptors involved in Alzheimer's disease? Neuroscience Letters, 306, 193–197.Google Scholar
Li, G. et al. (1995). Age at onset and familial risk in Alzheimer's disease. American Journal of Psychiatry, 152, 424–430.Google ScholarPubMed
Lin, G. F. et al. (2003). Polymorphism of alpha-estrogen receptor and aryl hydrocarbon receptor genes in dementia patients in Shanghai suburb. Acta Pharmacologica Sinica, 24, 651–656.Google Scholar
Ma, S. L., Tang, N. L., Lam, L. C. and Chiu, H. F. (2005). The association between promoter polymorphism of the interleukin-10 gene and Alzheimer's disease. Neurobiology of Aging, 26, 1005–1010.CrossRefGoogle ScholarPubMed
Maraganore, D. M. et al. (2006). Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease. Journal of the American Medical Association, 296, 661–670.CrossRefGoogle ScholarPubMed
Maruyama, H. et al. (2000). Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease. Archives of Neurology, 57, 236–240.CrossRefGoogle ScholarPubMed
McKhann, G. et al. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939–944.Google Scholar
Myers, A. et al. (2002). Full genome screen for Alzheimer disease: stage II analysis. American Journal of Medical Geneti, 114, 235–244.Google Scholar
Roodi, N. et al. (1995). Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. Journal of National Cancer Institute, 87, 446–451.Google Scholar
Shumaker, S. A. et al. (2004). Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. Journal of the American Medical Association, 291, 2947–2958.CrossRefGoogle ScholarPubMed
Slopien, R. et al. (2003). Influence of hormonal replacement therapy on the regional cerebral blood flow in postmenopausal women. Maturitas, 46, 255–262.Google Scholar
Srivastava, R. A. et al. (1997). Estrogen up-regulates apolipoprotein E (ApoE) gene expression by increasing ApoE mRNA in the translating pool via the estrogen receptor alpha-mediated pathway. Journal of Biological Chemistry, 272, 33360–33366.Google Scholar
Stephens, M., Smith, N. J. and Donnelly, P. (2001). A new statistical method for haplotype reconstruction from population data. American Journal of Human Genetics, 68, 978–989.CrossRefGoogle ScholarPubMed
Tang, M. X. et al. (1996). Effect of oestrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet, 348, 429–432.CrossRefGoogle ScholarPubMed
Tang, N. L., Pharoah, P. D., Ma, S. L. and Easton, D. F. (2006a). Evaluation of an algorithm of tagging SNPs selection by linkage disequilibrium. Clinical Biochemistry, 39, 240–243.Google Scholar
Tang, N. L. et al. (2006b). A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI) and adolescent idiopathic scoliosis: a study of 540 Chinese cases. Spine, 31, 2463–2468.CrossRefGoogle ScholarPubMed
Urabe, M. et al. (1996). Effect of estrogen replacement therapy on hepatic triglyceride lipase, lipoprotein lipase and lipids including apolipoprotein E in climacteric and elderly women. Endocrine Journal, 43, 737–742.Google Scholar
Usui, C. et al. (2006). No genetic association between the myeloperoxidase gene -463 polymorphism and estrogen receptor-alpha gene polymorphisms and Japanese sporadic Alzheimer's disease. Dementia and Related Geriatric Cognitive Disorders, 21, 296–299.Google Scholar
Wang, J. et al. (2007). Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women. Breast Cancer Research and Treatment.Google Scholar
Waring, S. C. et al. (1999). Postmenopausal estrogen replacement therapy and risk of AD: a population-based study. Neurology, 52, 965–970.Google Scholar
Yaffe, K., Lui, L. Y., Grady, D., Stone, K. and Morin, P. (2002). Estrogen receptor 1 polymorphisms and risk of cognitive impairment in older women. Biological Psychiatry, 51, 677–682.Google Scholar
Zavratnik, A., Prezelj, J., Kocijancic, A. and Marc, J. (2007). Exonic, but not intronic polymorphisms of ESR1 gene might influence the hypolipemic effect of raloxifene. Journal of Steroid Biochemistry and Molecular Biology, 104, 22–26.Google Scholar
Zhang, K. and Jin, L. (2003). HaploBlockFinder: haplotype block analyses. Bioinformatics, 19, 1300–1301.Google Scholar