PI-02 AGE AND OBESITY PROMOTE METHYLATION AND SUPPRESSION OF 5-ALPHA REDUCTASE 2–-IMPLICATIONS FOR PERSONALIZED THERAPY IN BPH

Abstract

You have accessJournal of UrologyPlenary Session I - Best Abstracts1 Apr 2015PI-02 AGE AND OBESITY PROMOTE METHYLATION AND SUPPRESSION OF 5-ALPHA REDUCTASE 2–-IMPLICATIONS FOR PERSONALIZED THERAPY IN BPH Seth Bechis, Alexander Otsetov, Rongbin Ge, Zongwei Wang, Mark Vangel, Chin-Lee Wu, Shahin Tabatabaei, and Aria Olumi Seth BechisSeth Bechis More articles by this author , Alexander OtsetovAlexander Otsetov More articles by this author , Rongbin GeRongbin Ge More articles by this author , Zongwei WangZongwei Wang More articles by this author , Mark VangelMark Vangel More articles by this author , Chin-Lee WuChin-Lee Wu More articles by this author , Shahin TabatabaeiShahin Tabatabaei More articles by this author , and Aria OlumiAria Olumi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2901AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 5α reductase 2 (5AR2) plays a key role in prostate growth and BPH progression. While 5α reductase inhibitors (5ARIs) are a main modality of treatment for men suffering bladder outlet obstruction secondary to BPH, over 30% of men are resistant to the therapeutic effects of 5ARIs. We have previously found that 30% of benign prostate samples do not express 5AR2, suggesting a mechanism for resistance to therapy. In this study we obtained prostate specimens from men undergoing surgical intervention for symptomatic BPH and sought to identify whether 5AR2 expression was linked to methylation of the 5AR2 gene promoter. We also assessed whether previously described clinical variables including age, obesity, cardiac risk factors, and prostate specific antigen (PSA) were associated with 5AR expression. METHODS We obtained BPH specimens from patients after surgical resection of the prostate. Immunohistochemistry was used to assess for 5AR2 protein expression. Methylation status of the gene promoter was determined using standard immunoprecipitation-based assays. We conducted univariate and multivariate statistical analyses to seek associations with clinical variables including age, body mass index (BMI), hypertension, hyperlipidemia, diabetes, prostate specific antigen (PSA), and prostate volume. RESULTS A total of 96 samples were included in the analysis. A majority (85%) of men were overweight (BMI 25-29) or obese (BMI≥30), and 80% of men who underwent surgical management of their bladder outlet obstruction were medically treated preoperatively with an α-blocker, 5ARI, or both. BMI and age were significantly correlated with methylation status of the 5AR2 gene promoter (p<0.05), whereas prostate volume, PSA, or use of BPH medication were not. Methylation status was highly correlated with 5AR protein expression (p<0.0001). As expected, prostate volume was associated with age and PSA (p<0.01). Using multivariate linear regression to form a predictive model, both age and BMI significantly predicted methylation status and protein expression (p<0.01). CONCLUSIONS Age and BMI correlate with methylation status of the 5AR2 gene promoter in symptomatic BPH samples. In addition, 5AR2 methylation is highly correlated with absence of protein expression. These results highlight the interplay between age, obesity and gene regulation. Our findings suggest the presence of an epigenetic signature for symptomatic BPH resistant to 5ARIs, which may be important for choosing appropriate treatment options. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e409 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Seth Bechis More articles by this author Alexander Otsetov More articles by this author Rongbin Ge More articles by this author Zongwei Wang More articles by this author Mark Vangel More articles by this author Chin-Lee Wu More articles by this author Shahin Tabatabaei More articles by this author Aria Olumi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...