{"paper_id":"1cee63ee-9633-47d6-a667-7bfe5bb5990f","body_text":"Published online Aug 27, 2013.\nhttps://doi.org/10.6118/jksm.2013.19.2.64\nAssociations between Estrogen Receptor Gene Polymorphisms and Endometriosis\nAbstract\nEndometriosis 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.\nFig. 1\nFour 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.\nFig. 2\nSchematic 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).\nTable 1\nSummary of PvuII polymorphism of estrogen receptor α (ERα) gene on endometriosis risk\nTable 2\nSummary of XbaI polymorphism of estrogen receptor α (ERα) gene on endometriosis risk\nTable 3\nSummary of RsaI polymorphism of estrogen receptor β (ERβ) gene associated with endometriosis risk\nTable 4\nSummary of AluI polymorphism of estrogen receptor β (ERβ) gene associated with endometriosis risk\nReferences\n-\nSensky TE, Liu DT. Endometriosis: associations with menorrhagia, infertility and oral contraceptives. Int J Gynaecol Obstet 1980;17:573–576.\n-\n-\nHouston DE. Evidence for the risk of pelvic endometriosis by age, race and socioeconomic status. Epidemiol Rev 1984;6:167–191.\n-\n-\nPellicano M, Magri G, Lacchi L. A case of ovarian endometriosis in late post-menopause. Clin Exp Obstet Gynecol 1994;21:57–58.\n-\n-\nCheck JH, Check ML, Kiefer D, Aikins J Jr. Ovarian cancer in a woman previously diagnosed with endometriosis and an extremely high serum CA-125 level. Clin Exp Obstet Gynecol 2001;28:83–85.\n-\n-\nChoi YM, Ku SY, Hwang KR, Lim YT, Park SH, Jun JK, et al. Estrogen receptor gene PvuII and XbaI polymorphism in patients with endometriosis. Korean J Obstet Gynecol 2003;46:1531–1536.\n-\n-\nKo HE, Whang DH, Noh JH, Kim YB. Association of progesterone receptor gene polymorphism (PROGINS) and estrogen receptor gene polymorphism with endometriosis in Korean population. Korean J Obstet Gynecol 2006;49:1471–1480.\n-\n-\nSampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol 1927;3:93–110.\n-\n-\nvan der Linden PJ. Endometriosis: a review on its pathogenesis. Front Biosci 1997;2:e48–e52.\n-\n-\nKüpker W, Felberbaum RE, Krapp M, Schill T, Malik E, Diedrich K. Use of GnRH antagonists in the treatment of endometriosis. Reprod Biomed Online 2002;5:12–16.\n-\n-\nBjörnström L, Sjöberg M. Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol Endocrinol 2005;19:833–842.\n-\n-\nWedrén S, Lovmar L, Humphreys K, Magnusson C, Melhus H, Syvänen AC, et al. Estrogen receptor alpha gene polymorphism and endometrial cancer risk--a case-control study. BMC Cancer 2008;8:322.\n-","source_license":"CC0","license_restricted":false}