Age and Obesity Promote Methylation and Suppression of 5a-Reductase 2: Implications for Personalized Therapy of XXXX .

@entity1 @entity407 @entity101 @entity28 @entity6 @entity1067 @entity1486
PURPOSE: In @entity1 with symptomatic @entity1067 5a-reductase inhibitors are a main modality of treatment. More than 30% of @entity1 do not respond to the therapeutic effects of 5a-reductase inhibitors. We have found that a third of adult prostate samples do not express 5a-reductase type 2 secondary to epigenetic modifications. We evaluated whether 5a-reductase type 2 expression in @entity1067 specimens from symptomatic @entity1 was linked to methylation of the 5a-reductase type 2 gene promoter. We also identified associations with age, @entity28 , cardiac risk factors and @entity1486 . MATERIALS AND METHODS: Prostate samples from @entity1 undergoing transurethral prostate resection were used. We determined 5a-reductase type 2 protein expression and gene promoter methylation status by common assays. Clinical variables included age, body mass index, @entity101 , @entity407 , @entity6 , @entity1486 and prostate volume. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling. RESULTS: Body mass index and age significantly correlated with methylation of the 5a-reductase type 2 gene promoter (p <0.05) whereas prostate volume, @entity1486 or @entity1067 medication did not correlate. Methylation highly correlated with 5a-reductase protein expression (p <0.0001). In a predictive model increasing age and body mass index significantly predicted methylation status and protein expression (p <0.01). CONCLUSIONS: Increasing age and body mass index correlate with increased 5a-reductase type 2 gene promoter methylation and decreased protein expression in @entity1 with symptomatic @entity1067 . These results highlight the  interplay among age, @entity28 and gene regulation. Our findings suggest an individualized epigenetic signature for symptomatic @entity1067 , which may be important to choose appropriate personalized treatment options.
