{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T05:12:13Z","timestamp":1739855533317,"version":"3.37.3"},"reference-count":24,"publisher":"PAGEPress Publications","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Ital Urol Androl"],"abstract":"<jats:p>Introduction and objectives: Being the most common disease in aged men, the etiology of benign prostatic hyperplasia (BPH) is not fully defined. Recent studies have reported that the association between BPH and metabolic genes is still inconsistent. A gene connected with BPH is SRD5AR2, whose polymorphisms, A49T and V89L, have distinct enzyme activity. This systematic review examines SRD5AR2 polymorphisms within two alleles (A49T and V89L), assessing their roles as prognostic indicators of malignancy, and response to medication. Materials and methods: We conducted a search on six different databases, including PubMed, Scopus, Wiley, ProQuest, Cochrane Central, and Science Direct using as string of keywords (BPH) AND [(rs523349) OR (V89L)] AND [(rs9282858) OR (A49T)]. We finally selected seven articles to be extracted. Quality appraisal of clinical trials was evaluated using the Joanna Briggs Institute Approach for systematic reviews. Results: We sorted nine clinical studies from various countries examining SRDA52 polymorphism and its association of BPH and prostate cancer. About V89L we found that the \"LL\" genotype, indicating reduced 5\u03b1-reductase activity, is linked to a lower BPH risk, while the \"VV\" genotype may slightly increase BPH risk. About A49T, compared to \u201cAA\u201d genotype, \u201cAT\u201d tends to be associated to higher risk in developing prostate cancer. A49T polymorphism does not show any effect on medical treatment while V89L showed a protective effect on the clinical progression of BPH when treated with 5a-reductase inhibitors, aadrenergic receptor antagonists, and alpha blockers. Conclusions: SRD5A2 polymorphisms could be a good indicator for prognostic malignancy and a potential tool for personalized medicine of BPH. The findings strongly support the recommendation for further study about SRD5AR2 to enhance its use for screening and prevention and to optimize the medical treatment of BPH.<\/jats:p>","DOI":"10.4081\/aiua.2025.13318","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T15:22:41Z","timestamp":1739805761000},"source":"Crossref","is-referenced-by-count":0,"title":["A comprehensive systematic review of studies on the potential of A49T and V89L polymorphism in SRD5AR2 as high susceptibility gene association with benign prostate hyperplasia and prostate cancer"],"prefix":"10.4081","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4123-980X","authenticated-orcid":false,"given":"Revina","family":"Maharani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9234-4382","authenticated-orcid":false,"given":"Hotma","family":"Lestari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0542-5941","authenticated-orcid":false,"given":"Putra Mahakarya","family":"Dewa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3317-1602","authenticated-orcid":false,"given":"Dewangga","family":"Yudisthira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasim","family":"Amar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Besut","family":"Daryanto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2549","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"166660","unstructured":"Roehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol. 2005; 7(Suppl 9):S3-S14."},{"key":"166661","doi-asserted-by":"crossref","unstructured":"Goodarzi D, Cyrus A, Khoddami Vishteh HR, et al. Effect of celecoxib on benign prostatic hyperplasia: Results of a preliminary study. Urol Scie. 2011; 22:147-150.","DOI":"10.1016\/j.urols.2011.07.001"},{"key":"166662","unstructured":"Middleton LW, Shen Z, Varma S, et al. Genomic analysis of benign prostatic hyperplasia implicates cellular re-landscaping in"},{"key":"166663","unstructured":"disease pathogenesis. JCI Insight. 2019; 5:e129749."},{"key":"166664","doi-asserted-by":"crossref","unstructured":"Li Q, Zhu Y, He J, et al. Steroid 5-alpha-reductase type 2 (SRD5A2) V89L and A49T polymorphisms and sporadic prostate cancer risk: a meta-analysis. Molecular biology reports 2013; 40:3597-3608.","DOI":"10.1007\/s11033-012-2434-x"},{"key":"166665","unstructured":"Choubey VK, Sankhwar SN, Carlus SJ, et al. SRD5A2 gene polymorphisms and the risk of benign prostatic hyperplasia but not"},{"key":"166666","doi-asserted-by":"crossref","unstructured":"prostate cancer. Asian Pac J Cancer Prev. 2015; 16:1033-1036.","DOI":"10.7314\/APJCP.2015.16.3.1033"},{"key":"166667","doi-asserted-by":"crossref","unstructured":"Salam MT, Ursin G, Skinner EC, et al. Associations between polymorphisms in the steroid 5-alpha reductase type II (SRD5A2) gene and benign prostatic hyperplasia and prostate cancer. Urol Oncol. 2005; 23:246-253.","DOI":"10.1016\/j.urolonc.2004.12.014"},{"key":"166668","doi-asserted-by":"crossref","unstructured":"Zeng XT, Su XJ, Li S, et al. Association between SRD5A2 rs523349 and rs9282858 Polymorphisms and Risk of Benign Prostatic Hyperplasia: A Meta-Analysis. Front Physiol. 2017; 8:688.","DOI":"10.3389\/fphys.2017.00688"},{"key":"166669","doi-asserted-by":"crossref","unstructured":"Price DK, Chau CH, Till C, et al. Association of androgen metabolism gene polymorphisms with prostate cancer risk and androgen concentrations: Results from the Prostate Cancer Prevention Trial. Cancer. 2016; 122:2332-2340.","DOI":"10.1002\/cncr.30071"},{"key":"166670","doi-asserted-by":"crossref","unstructured":"Elzanaty S, Giwercman YL, Giwercman A. Significant impact of 5alpha-reductase type 2 polymorphisms on sperm concentration and motility. Int J Androl. 2006; 29:414-20.","DOI":"10.1111\/j.1365-2605.2005.00625.x"},{"key":"166671","doi-asserted-by":"crossref","unstructured":"Neslund-Dudas C, Bock CH, Monaghan K, et al. SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness. Prostate 2007; 67:1654-1663.","DOI":"10.1002\/pros.20625"},{"key":"166672","unstructured":"Allen NE, Forrest MS, Key TJ. The association between polymorphisms in the CYP17 and 5\u03b1-reductase (SRD5A2) genes and serum androgen concentrations in men. Cancer Epidemiol Biomarkers Prev. 2001; 10:185-9."},{"key":"166673","unstructured":"Van Gils CH, Onland-Moret NC, Roest M, et al. The V89L Polymorphism in the 5-\u03b1-Reductase Type 2 Gene and Risk of Breast"},{"key":"166674","unstructured":"Cancer. Cancer Epidemiol Biomarkers Prev. 2003; 12:1194-9."},{"key":"166675","doi-asserted-by":"crossref","unstructured":"Wang C, Tao W, Chen Q, et al. SRD5A2 V89L polymorphism and prostate cancer risk: A meta-analysis. Prostate. 2010; 70:170-8.","DOI":"10.1002\/pros.21050"},{"key":"166676","doi-asserted-by":"crossref","unstructured":"Li J, Coates RJ, Gwinn M, Khoury MJ. Steroid 5-\u03b1-reductase type 2 (SRD5a2) gene polymorphisms and risk of prostate cancer: A HuGE review. Am J Epidemiol. 2010; 171:1-13.","DOI":"10.1093\/aje\/kwp318"},{"key":"166677","unstructured":"Giwercman YL, Abrahamsson PA, Giwercman A, et al. The 5alpha-reductase type II A49T and V89L high-activity allelic variants"},{"key":"166678","doi-asserted-by":"crossref","unstructured":"are more common in men with prostate cancer compared with the general population. Eur Urol. 2005; 48:679-85.","DOI":"10.1016\/j.eururo.2005.06.011"},{"key":"166679","unstructured":"Tekin Neijmann S, Kural A, Tinay I, et al. Association of missense substitution of A49T and V89L in the SRD5A2 gene with"},{"key":"166680","doi-asserted-by":"crossref","unstructured":"prostate cancer in Turkish patients. Turk. J. Biochem. 2017; 42:37-43.","DOI":"10.1515\/tjb-2016-0164"},{"key":"166681","doi-asserted-by":"crossref","unstructured":"Konwar R, Chattopadhyay N, Bid HK. Genetic polymorphism and pathogenesis of benign prostatic hyperplasia (BPH). BJU Int. 2008; 5:536-44.","DOI":"10.1111\/j.1464-410X.2008.07667.x"},{"key":"166682","doi-asserted-by":"crossref","unstructured":"Lunn RM, Bell DA, Mohler JL, Taylor JA. Prostate cancer risk and polymorphism in 17 hydroxylase (CYP17) and steroid reductase (SRD5A2). Carcinogenesis. 1999; 20:1727-31.","DOI":"10.1093\/carcin\/20.9.1727"},{"key":"166683","doi-asserted-by":"crossref","unstructured":"Daryanto B, Naim HY, Budaya TN. The Effect of Tamsulosin, Dutasteride Monotherapy and Tamsulosin-Dutasteride Combination on Prostate Smooth Muscle Contractility in BPH Model Wistar Strain Rattus Novergicus. Med. Arch. 2023;77:13.","DOI":"10.5455\/medarh.2023.77.13-17"}],"container-title":["Archivio Italiano di Urologia e Andrologia"],"original-title":[],"link":[{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/download\/13318\/12862","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/download\/13318\/12862","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T15:22:51Z","timestamp":1739805771000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/view\/13318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,17]]},"references-count":24,"URL":"https:\/\/doi.org\/10.4081\/aiua.2025.13318","relation":{},"ISSN":["2282-4197","1124-3562"],"issn-type":[{"value":"2282-4197","type":"electronic"},{"value":"1124-3562","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2,17]]}}}