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Estrogen receptor α gene polymorphisms and risk of Alzheimer’s disease: evidence from a meta-analysis

Authors Cheng D, Liang B, Hao Y, Zhou W

Received 10 April 2014

Accepted for publication 2 May 2014

Published 30 June 2014 Volume 2014:9 Pages 1031—1038


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Daye Cheng,1 Bin Liang,2 Yiwen Hao,1 Wenling Zhou1

1Department of Transfusion, First Hospital of China Medical University, Shenyang, 2Department of Clinical Laboratory, High Vocational Technological College, China Medical University, Shenyang, People’s Republic of China

Objective: Human estrogen receptor α (ESR1), a member of the nuclear receptor superfamily of ligand-activated transcription factors, is one of the key mediators of hormonal response in estrogen-sensitive tissues. Accumulating evidence has demonstrated that two of the most widely studied single-nucleotide polymorphisms in ESR1 – PvuII (T/C, rs223493) and Xbal (A/G, rs9340799) – are possibly associated with Alzheimer’s disease (AD). However, individual study results are still controversial.
Materials and methods: We searched PubMed, Embase, Web of Science, Science Direct, SpringerLink, and the Chinese National Knowledge Infrastructure databases for eligible studies assessing the association of ESR1 polymorphisms and AD risk (last search performed in November 2013). Thereafter, a meta-analysis of 13,192 subjects from 18 individual studies was conducted to evaluate the association between ESR1 polymorphisms and susceptibility to AD.
Results: The results indicated that a significant association was found between the ESR1 PvuII polymorphism and AD risk in Caucasian populations (CC + CT versus TT, odds ratio [OR] 1.14, 95% confidence interval [CI] 1.02–1.28, P=0.03; CT versus TT, OR 1.16, 95% CI 1.02–1.31, P=0.02), whereas no evidence of association was found in Asian populations. Nevertheless, we did not find any significant association between the ESR1 XbaI polymorphism and AD risk for any model in Caucasian and Asian populations (all P>0.05).
Conclusion: Based on this meta-analysis, we conclude that the ESR1 PvuII polymorphism might be a risk factor in AD development in Caucasian populations, not in Asian populations. Further confirmation is needed from better-designed and larger studies.

Keywords: Alzheimer’s disease, estrogen receptor, polymorphism, meta-analysis

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