Association between polymorphisms of estrogen receptor 2 and benign prostatic hyperplasia

Kim,Su  Kang; Chung,Joo‑Ho; Park,Hyun  Chul; Kim,Jun  Ho; Ann,Jae  Hong; Park,Hun  Kuk; Lee,Sang   Hyup; Yoo,Koo  Han; Lee,Byung‑Cheol; Kim,Young  Ock

doi:10.3892/etm.2015.2755

Association between polymorphisms of estrogen receptor 2 and benign prostatic hyperplasia

Authors:
- Su Kang Kim
- Joo‑Ho Chung
- Hyun Chul Park
- Jun Ho Kim
- Jae Hong Ann
- Hun Kuk Park
- Sang Hyup Lee
- Koo Han Yoo
- Byung‑Cheol Lee
- Young Ock Kim
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Affiliations: Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Department of Biomedical Engineering and Healthcare Industry Research Institute, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Department of Urology, School of Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University, Seoul 130‑701, Republic of Korea, Herbal Crop Utilization Research Team, Department of Medicinal Crop Research, Rural Administration, Soi‑myeon, Eumseong‑gun 369‑873, Republic of Korea
Published online on: September 21, 2015 https://doi.org/10.3892/etm.2015.2755
Pages: 1990-1994

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Abstract

Estrogens and estrogen receptors (ESRs) have been implicated in the stimulation of aberrant prostate growth and the development of prostate diseases. The aim of the present study was to investigate four single nucleotide polymorphisms (SNPs) of the ESR2 gene in order to examine whether ESR2 is a susceptibility gene for benign prostatic hyperplasia (BPH). In order to evaluate whether an association exists between ESR2 and BPH risk, four polymorphisms [rs4986938 (intron), rs17766755 (intron), rs12435857 (intron) and rs1256049 (Val328Val)] of the ESR2 gene were genotyped by direct sequencing. A total of 94 patients with BPH and 79 control subjects were examined. SNPStats and Haploview version 4.2 we used for the genetic analysis. Multiple logistic regression models (codominant1, codominant2, dominant, recessive and log‑additive) were produced in order to obtain the odds ratio, 95% confidence interval and P‑value. Three SNPs (rs4986938, rs17766755 and rs12435857) showed significant associations with BPH (rs4986938, P=0.015 in log‑additive model; rs17766755, P=0.033 in codominant1 model, P=0.019 in dominant model and P=0.020 in log‑additive model; rs12435857, P=0.023 in dominant model and P=0.011 in log‑additive model). The minor alleles of these SNPs increased the risk of BPH, and the AAC haplotype showed significant association with BPH (χ2=6.34, P=0.0118). These data suggest that the ESR2 gene may be associated with susceptibility to BPH.

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1	Karatzas A, Tzortzis V, Giannatou E, Gravas S, Zachos I, Oeconomou A, Melekos M and Tsezou A: Lack of association between the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphism and the risk of benign prostatic hyperplasia in Caucasian men. Mol Biol Rep. 40:6665–6669. 2013. View Article : Google Scholar : PubMed/NCBI
2	Roehrborn CG and Rosen RC: Medical therapy options for aging men with benign prostatic hyperplasia: Focus on alfuzosin 10 mg once daily. Clin Interv Aging. 3:511–524. 2008.PubMed/NCBI
3	Roehrborn CG: Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Med Clin North Am. 95:87–100. 2011. View Article : Google Scholar : PubMed/NCBI
4	Bianco JJ, McPherson SJ, Wang H, Prins GS and Risbridger GP: Transient neonatal estrogen exposure to estrogen-deficient mice (aromatase knockout) reduces prostate weight and induces inflammation in late life. Am J Pathol. 168:1869–1878. 2006. View Article : Google Scholar : PubMed/NCBI
5	Prins GS and Korach KS: The role of estrogens and estrogen receptors in normal prostate growth and disease. Steroids. 73:233–244. 2008. View Article : Google Scholar : PubMed/NCBI
6	McPherson SJ, Ellem SJ and Risbridger GP: Estrogen-regulated development and differentiation of the prostate. Differentiation. 76:660–670. 2008. View Article : Google Scholar : PubMed/NCBI
7	Menasce LP, White GR, Harrison CJ and Boyle JM: Localization of the estrogen receptor locus (ESR) to chromosome 6q25.1 by FISH and a simple post-FISH banding technique. Genomics. 17:263–265. 1993. View Article : Google Scholar : PubMed/NCBI
8	Weihua Z, Makela S, Andersson LC, Salmi S, Saji S, Webster JI, Jensen EV, Nilsson S, Warner M and Gustafsson JA: A role for estrogen receptor beta in the regulation of growth of the ventral prostate. Proc Natl Acad Sci USA. 98:6330–6335. 2001. View Article : Google Scholar : PubMed/NCBI
9	Prins GS, Marmer M, Woodham C, Chang W, Kuiper G, Gustafsson JA and Birch L: Estrogen receptor-beta messenger ribonucleic acid ontogeny in the prostate of normal and neonatally estrogenized rats. Endocrinology. 139:874–883. 1998. View Article : Google Scholar : PubMed/NCBI
10	Krege JH, Hodgin JB, Couse JF, Enmark E, Warner M, Mahler JF, Sar M, Korach KS, Gustafsson JA and Smithies O: Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci USA. 95:15677–15682. 1998. View Article : Google Scholar : PubMed/NCBI
11	Ban JY and Yoo KH: Promoter polymorphism (rs12770170, −184C/T) of microseminoprotein, beta as a risk factor for benign prostatic hyperplasia in Korean population. Int Neurourol J. 18:63–67. 2014. View Article : Google Scholar : PubMed/NCBI
12	Yoo KH, Kim SK, Chung JH and Chang SG: Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia. Asian J Androl. 12:690–696. 2010. View Article : Google Scholar : PubMed/NCBI
13	Ryan J, Carrière I, Amieva H, Rouaud O, Berr C, Ritchie K, Scarabin PY and Ancelin ML: Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women. Eur Neuropsychopharmacol. 23:1763–1768. 2013. View Article : Google Scholar : PubMed/NCBI
14	Marini H, Curro M, Adamo EB, Polito F, Ferlazzo N, Bitto A, Atteritano M, D'Anna R, Alibrandi A, Altavilla D, et al: The ESR2 AluI 1730G>A (rs4986938) gene polymorphism is associated with fibrinogen plasma levels in postmenopausal women. Gene. 508:206–210. 2012. View Article : Google Scholar : PubMed/NCBI
15	Kristiansen W, Andreassen KE, Karlsson R, Aschim EL, Bremnes RM, Dahl O, Fosså SD, Klepp O, Langberg CW, Solberg A, et al: Gene variations in sex hormone pathways and the risk of testicular germ cell tumour: A case-parent triad study in a Norwegian-Swedish population. Hum Reprod. 27:1525–1535. 2012. View Article : Google Scholar : PubMed/NCBI
16	Yang TL, Xiong DH, Guo Y, Recker RR and Deng HW: Comprehensive association analyses of IGF1, ESR2 and CYP17 genes with adult height in Caucasians. Eur J Hum Genet. 16:1380–1387. 2008. View Article : Google Scholar : PubMed/NCBI
17	Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, et al: The structure of haplotype blocks in the human genome. Science. 296:2225–2229. 2002. View Article : Google Scholar : PubMed/NCBI
18	Schuler S, Lattrich C, Skrzypczak M, Fehm T, Ortmann O and Treeck O: Polymorphisms in the promoter region of ESR2 gene and susceptibility to ovarian cancer. Gene. 546:283–287. 2014. View Article : Google Scholar : PubMed/NCBI
19	Gu Z, Wang G and Chen W: Estrogen receptor alpha gene polymorphisms and risk of prostate cancer: A meta-analysis involving 18 studies. Tumour Biol. 35:5921–5930. 2014. View Article : Google Scholar : PubMed/NCBI
20	Chattopadhyay S, Siddiqui S, Akhtar MS, Najm MZ, Deo SV, Shukla NK and Husain SA: Genetic polymorphisms of ESR1, ESR2, CYP17A1 and CYP19A1 and the risk of breast cancer: A case control study from North India. Tumour Biol. 35:4517–4527. 2014. View Article : Google Scholar : PubMed/NCBI
21	Attia DM and Ederveen AG: Opposing roles of ERα and ERβ in the genesis and progression of adenocarcinoma in the rat ventral prostate. Prostate. 72:1013–1022. 2012. View Article : Google Scholar : PubMed/NCBI
22	Hammarsten J, Damber JE, Karlsson M, Knutson T, Ljunggren O, Ohlsson C, Peeker R, Smith U and Mellström D: Insulin and free oestradiol are independent risk factors for benign prostatic hyperplasia. Prostate Cancer Prostatic Dis. 12:160–165. 2009. View Article : Google Scholar : PubMed/NCBI
23	García-Flórez M, Oliveira CA and Carvalho HF: Early effects of estrogen on the rat ventral prostate. Braz J Med Biol Res. 38:487–497. 2005. View Article : Google Scholar : PubMed/NCBI
24	McPherson SJ, Hussain S, Balanathan P, Hedwards SL, Niranjan B, Grant M, Chandrasiri UP, Toivanen R, Wang Y, Taylor RA and Risbridger GP: Estrogen receptor-beta activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFalpha mediated. Proc Natl Acad Sci USA. 107:3123–3128. 2010. View Article : Google Scholar : PubMed/NCBI
25	Sadee W, Wang D, Papp AC, Pinsonneault JK, Smith RM, Moyer RA and Johnson AD: Pharmacogenomics of the RNA world: Structural RNA polymorphisms in drug therapy. Clin Pharmacol Ther. 89:355–365. 2011. View Article : Google Scholar : PubMed/NCBI