SRD5A1 and SRD5A2 are Associated with Treatment for Benign Prostatic Hyperplasia with the Combination of 5α-Reductase Inhibitors and α-Adrenergic Receptor Antagonists

No AccessJournal of UrologyAdult Urology1 Aug 2013SRD5A1 and SRD5A2 are Associated with Treatment for Benign Prostatic Hyperplasia with the Combination of 5α-Reductase Inhibitors and α-Adrenergic Receptor Antagonists Xin Gu, Rong Na, Tao Huang, Li Wang, Sha Tao, Lu Tian, Zhuo Chen, Yang Jiao, Jian Kang, Siqun Zheng, Jianfeng Xu, Jielin Sun, and Jun Qi Xin GuXin Gu Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China Equal study contribution. More articles by this author , Rong NaRong Na Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina Equal study contribution. More articles by this author , Tao HuangTao Huang Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China More articles by this author , Li WangLi Wang Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author , Sha TaoSha Tao Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author , Lu TianLu Tian Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author , Zhuo ChenZhuo Chen Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author , Yang JiaoYang Jiao Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China Deceased. More articles by this author , Jian KangJian Kang Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China More articles by this author , Siqun ZhengSiqun Zheng Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author , Jianfeng XuJianfeng Xu Fudan-VARI Center for Genetic Epidemiology, Fudan University, Shanghai, People's Republic of China Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author , Jielin SunJielin Sun Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author , and Jun QiJun Qi Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.03.024AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. Materials and Methods: We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. Results: The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). Conclusions: SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment. References 1 : Benign prostatic hyperplasia and prostate cancer: an overview for primary care physicians. Int J Clin Pract2010; 64: 1740. Google Scholar 2 : The pathophysiology of benign prostatic hyperplasia. J Androl1991; 12: 356. Medline, Google Scholar 3 : Quality-of-life impact of lower urinary tract symptom severity: results from the Health Professionals Follow-up Study. Urology2002; 59: 245. Google Scholar 4 : Health-related quality of life associated with lower urinary tract symptoms in four countries. Urology1998; 51: 428. Google Scholar 5 : Book review: Campbell's Urology, 7th edition. (3 volume set). Ann Saudi Med1998; 18: 570. Google Scholar 6 : An overview on 5alpha-reductase inhibitors. Steroids2010; 75: 109. Google Scholar 7 : Actions of 5alpha-reductase inhibitors on the epididymis. Mol Cell Endocrinol2006; 250: 190. Google Scholar 8 : The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones. J Urol2005; 173: 2010. Link, Google Scholar 9 : The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med2003; 349: 2387. Google Scholar 10 : Long-term treatment with finasteride improves clinical progression of benign prostatic hyperplasia in men with an enlarged versus a smaller prostate: data from the MTOPS trial. J Urol2011; 185: 1369. Link, Google Scholar 11 : Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample. World J Urol2011; 29: 143. Google Scholar 12 : Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS). BJU Int2011; 108: 388. Google Scholar 13 : Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II. Pharmacogenetics2000; 10: 407. Google Scholar 14 Ma Z, Hu Q, Chen Z et al: Systematic evaluation of bladder cancer risk-associated single-nucleotide polymorphisms in a Chinese population. Mol Carcinog, Epub ahead of print June 18, 2012. Google Scholar 15 : Haploview: Visualization and analysis of SNP genotype data. Cold Spring Harb Protoc2009; 2009. pdb.ip71. Google Scholar 16 : PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet2007; 81: 559. Google Scholar 17 : Genetic variability of the human SRD5A2 gene: implications for prostate cancer risk. Cancer Res1995; 55: 3973. Google Scholar 18 : Associations between polymorphisms in the steroid 5-alpha reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer. Urol Oncol2005; 23: 246. Google Scholar 19 : Polymorphisms in the 5alpha reductase type 2 gene and urologic measures of BPH. Prostate2005; 62: 380. Google Scholar 20 : A case-based evaluation of SRD5A1, SRD5A2, AR, and ADRA1A as candidate genes for severity of BPH. Pharmacogenomics J2004; 4: 251. Google Scholar 21 : Association of polymorphisms within androgen receptor, 5alpha-reductase, and PSA genes with prostate volume, clinical parameters, and endocrine status in elderly men. Prostate2002; 52: 130. Google Scholar 22 : Genetic impact on prostate anatomical variability during ageing: role of CYP17, SRD5A2 and androgen receptor genes polymorphisms. BJU Int2007; 100: 679. Google Scholar 23 : Associations of polymorphisms in HPC2/ELAC2 and SRD5A2 genes with benign prostate hyperplasia in Turkish men. Asian Pac J Cancer Prev2011; 12: 731. Google Scholar 24 : Genetic polymorphisms in the androgen receptor and type II 5 alpha-reductase genes in prostate enlargement. J Urol2001; 166: 1560. Link, Google Scholar 25 : Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population. J Urol2003; 169: 2378. Link, Google Scholar 26 : Small but influential: the role of microRNAs on gene regulatory network and 3′UTR evolution. J Genet Genomics2009; 36: 1. Google Scholar 27 : MicroRNAs: target recognition and regulatory functions. Cell2009; 136: 215. Google Scholar 28 : MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol2011; 3: 83. Google Scholar 29 : MicroRNA biogenesis, functionality and cancer relevance. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub2006; 150: 205. Google Scholar © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 190Issue 2August 2013Page: 615-619Supplementary Materials Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Keywordsprostatic hyperplasiapolymorphism, single nucleotideSRD5A1 protein, humanprostateSRD5A2 protein, humanAcknowledgmentsDedicated to the memory of Dr. Yang Jiao, Xinhua Hospital, Shanghai, People's Republic of China.MetricsAuthor Information Xin Gu Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China Equal study contribution. More articles by this author Rong Na Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina Equal study contribution. More articles by this author Tao Huang Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China More articles by this author Li Wang Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author Sha Tao Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author Lu Tian Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author Zhuo Chen Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author Yang Jiao Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China Deceased. More articles by this author Jian Kang Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China More articles by this author Siqun Zheng Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author Jianfeng Xu Fudan-VARI Center for Genetic Epidemiology, Fudan University, Shanghai, People's Republic of China Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author Jielin Sun Center for Cancer Genomics and Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine, Winston-Salem, North Carolina More articles by this author Jun Qi Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China More articles by this author Expand All Advertisement PDF downloadLoading ...