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Mun, Kim, Kim, Hwang, and Jang: Associations between Estrogen Receptor Gene Polymorphisms and Endometriosis
Review Article

The Journal of Korean Society of Menopause 2013; 19(2): 64-73.

Published online: 27 August 2013

DOI: https://doi.org/10.6118/jksm.2013.19.2.64

Associations between Estrogen Receptor Gene Polymorphisms and Endometriosis

Myung Jin Mun, M.S.1, 2, Jin-Ho Kim, M.S.1, 2, Tae-Hee Kim, M.D., Ph.D.3, Ji-Young Hwang, Ph.D.1, Won-Choeul Jang, Ph.D.1, 2

1Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Korea.

2Department of Chemistry, School of Natural Science, Dankook University, Cheonan, Korea.

3Department of Obstetrics and Gynecology, College of Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.

Address for Correspondence: Ji-Young Hwang, Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 29 Anseo-dong, Cheonan 330-714, Korea. Tel: +82-41-550-3084, Fax: +82-41-559-7840, jy.hwang@dankook.ac.kr

Received 9 July 2013       Revised 22 July 2013       Accepted 22 July 2013

Copyright © 2013 by The Korean Society of Menopause

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/).

Abstract

Endometriosis is common estrogen-related gynecological diseases related to interactions of dietary, genetic causes, social and environmental factors. The high prevalence approaches 5-15% in premenopausal women and 30% in infertile women, and it is unusual to occur after the onset of menopause. In this review, the gene polymorphisms of estrogen receptor (ER) α and βre-lated to the risks of endometriosis were investigated through statistical analysis by using the gene polymorphism for the risks of the disease examined trends. The polymorphism of ERα-PvuII in Europe tends to increase the risk of endometriosis and, ERα-XbaI polymorphisms in both Asia and Europe have a slightly increased risk of endometriosis. In the case of ERβ-RsaI, the risk of endometriosis increases in Brazil, while the polymorphism of ERβ-AluI reduces the disease risks in Asia. Polymorphism studies on ER associated with the risk of endometriosis in Asia and Europe showed that those polymorphisms may be used to predict the high or low risks of endometriosis, and potentially used for prevention, therapy or prognosis of endometriosis. Further studies on interacting with more related genes and environmental factors may provide a better understanding of associations between estrogen receptor gene polymorphisms and endometriosis.

Keywords: Endometriosis, Estrogens, Polymorphism genetic, Receptors estrogen

Figures and Tables

Fig. 1
Four major mechanisms of estrogen and estrogen receptors (ER). (I) Classical ligand-dependent genomic target with direct binding actions; estrogen-ER complex directly binds to estrogen response element (ERE) in the target genes and then leads to regulations of transcription activity. (II) Non-classical ligand-dependent genomic target with indirect binding actions; estrogen-bound ER dimers interact with transcription factors, followed by regulations of target genes. (III) Ligand-dependent, non-genomic target actions; estrogen-ER complex phosphorylation (P) to target proteins lead to functions of proteins in cytoplasm or activations of transcription factor (TF) through phosphorylation in nucleus. (IV) Non-classical ligand-independent genomic target with direct binding actions; activation of growth factor receptor (GFR) phosphorylates ER to bind and regulate the target genes. The abbreviation are as follows; ER, ERE, TF, P, growth factor (GF), GFR, heat shock protein (HSP), RNA polymerase II (POL II) and coactivator (CoA). The dashed lines represent multiple pathways.
jksm-19-64-g001
Fig. 2
Schematic representation of estrogen receptors (ER). ERα and ERβ variants show DNA-binding domains (DBD), hinge regions, ligand-binding domains (LBD) and two transcriptional activation functions, AF-1 and AF-2. Four major single nucleotide polymorphisms studied in this review are shown in the boxes: ERα-PvuII (rs2234693; c.435-397T > C), ERα-XbaI (rs9340799; c.453-351A > G), ERβ-RsaI (rs1256049; c.984G > A) and ERβ-AluI (rs4986938; c.4106+1872G > A).
jksm-19-64-g002
Table 1
Summary of PvuII polymorphism of estrogen receptor α (ERα) gene on endometriosis risk
jksm-19-64-i001

*χ2 value of each HWE. The red line indicates the OR number 1 and the x-axis is log-scaled.

OR: odds ratio, CI: confidence interval, HWE: Hardy-Weinberg equilibrium, NA: not applicable.

Table 2
Summary of XbaI polymorphism of estrogen receptor α (ERα) gene on endometriosis risk
jksm-19-64-i002

OR: odds ratio, CI: confidence interval, HWE: Hardy-Weinberg equilibrium, NA: not applicable

Table 3
Summary of RsaI polymorphism of estrogen receptor β (ERβ) gene associated with endometriosis risk
jksm-19-64-i003

CI: confidence interval, OR: odds ratio, HWE: Hardy-Weinberg equilibrium, NA: not applicable

Table 4
Summary of AluI polymorphism of estrogen receptor β (ERβ) gene associated with endometriosis risk
jksm-19-64-i004

CI: confidence interval, HWE: Hardy-Weinberg equilibrium, OR: odds ratio, NA: not applicable

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