PURPOSE: 5α reductase inhibitors (5ARIs) are a main modality of treatment for men suffering from symptomatic benign prostatic hyperplasia (BPH).
Over 30% of men do not respond to the therapeutic effects of 5ARIs. We have found that 1/3 of adult prostate samples do not express 5AR2 secondary to epigenetic modifications. We sought to evaluate whether 5AR2 expression in BPH specimens of symptomatic men was linked to methylation of the 5AR2 gene promoter and identify associations with age, obesity, cardiac risk factors, and prostate specific antigen (PSA).
MATERIALS AND METHODS: Prostate samples from men undergoing transurethral prostate resection were used. 5AR2 protein expression and gene promoter methylation status were determined by common assays. Clinical variables included age, body mass index (BMI), hypertension, hyperlipidemia, diabetes, PSA, and prostate volume. Univariate and multivariate statistical analyses were performed, followed by stepwise logistic regression modeling.
RESULTS: BMI and age were significantly correlated with methylation of the 5AR2 gene promoter (p< 0.05), whereas prostate volume, PSA, or use of BPH medication were not. Methylation was highly correlated with 5AR protein expression (p< 0.0001). In a predictive model, both increasing age and BMI significantly predicted methylation status and protein expression (p< 0.01).
CONCLUSIONS: Increasing age and BMI correlate with increased 5AR2 gene promoter methylation and decreased protein expression in men with symptomatic BPH. These results highlight the interplay between age, obesity and gene regulation. Our findings suggest the presence of an individualized epigenetic signature for symptomatic BPH, which may be important for choosing appropriate personalized treatment options.
Written by:
Bechis SK, Otsetov AG, Ge R, Wang Z, Vangel MG, Wu CL, Tabatabaei S, Olumi AF. Are you the author?
Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Radiology and Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Reference: J Urol. 2015 Apr 24. pii: S0022-5347(15)03861-6.
doi: 10.1016/j.juro.2015.04.079
PubMed Abstract
PMID: 25916673