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Role of CYP17 rs743572 Polymorphism in Benign Prostatic Hyperplasia: A Multivariate Integrated Analysis.

ABSTRACT: Objective: Many published studies have investigated the association between CYP17 rs743572 polymorphism and benign prostatic hyperplasia (BPH) susceptibility but have yielded inconsistent results. Hence, we performed this meta-analysis using the multivariate statistic method to address a more precise association. Methods: Case-control or cohort studies with adequate genotype distribution or minor allele frequency (MAF) were identified by searching the PubMed, Embase, and Web of Science databases up to December, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the association between CYP17 rs743572 polymorphism and BPH susceptibility. Results: Pooled MAFs of 13 studies were 37% in Caucasians and 56% in Orientals, respectively. Pooled results of 8 studies suggested that CYP17 rs743572 was not associated with the BPH susceptibility in the overall population (OR = 0.98, 95% CI: 0.80-1.20 for A2 vs. A1; OR = 0.99, 95% CI: 0.79-1.25 for A1/A2 vs. A1/A1; OR = 0.97, 95% CI: 0.62-1.53 for A2/A2 vs. A1/A1). Sensitivity analysis showed the results were robust. Subgroup analysis based on ethnicity suggested that, in Orientals, A2 allele carriers had a 28% lower risk of developing BPH compared with A1 allele carriers, and the risk of BPH is 47% lower in A2/A2 genotype carriers compared with A1/A1 genotype carriers. No significant association was observed in Caucasians. Conclusion: In conclusion, our study indicates a negative association between CYP17 and BPH in Orientals. However, due to limited sample size, the conclusion should be interpreted with caution.

SUBMITTER: Weng H

PROVIDER: S-EPMC6599153 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Role of CYP17 rs743572 Polymorphism in Benign Prostatic Hyperplasia: A Multivariate Integrated Analysis.

Weng Hong H Fang Cheng C Geng Pei-Liang PL Jin Ying-Hui YH Zeng Xian-Tao XT Wang Xing-Huan XH

Frontiers in physiology 20190621

<b>Objective:</b> Many published studies have investigated the association between CYP17 rs743572 polymorphism and benign prostatic hyperplasia (BPH) susceptibility but have yielded inconsistent results. Hence, we performed this meta-analysis using the multivariate statistic method to address a more precise association. <b>Methods:</b> Case-control or cohort studies with adequate genotype distribution or minor allele frequency (MAF) were identified by searching the PubMed, Embase, and Web of Sci ...[more]

PMID: 31293443

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Project description:BackgroundThe volume and thickness of intravesical prostatic protrusion and other characteristics of benign prostatic hyperplasia have not been investigated. We determine the effects of age and prostate volume on anatomical features of benign prostatic hyperplasia using three-dimensional measurement in this study.MethodsThis retrospective study included a total of 98 patients with benign prostatic hyperplasia. Three-dimensional models of prostate, central gland, peripheral zone, intravesical prostatic protrusion, prostatic urethra and bladder were reconstructed according to pelvic T2-weighted magnetic resonance imaging of these patients. The models were used to measure the intravesical prostatic protrusion volume, intravesical prostatic protrusion thickness, intravesical prostatic protrusion index, intravesical prostatic protrusion, prostate volume, peripheral zone volume, peripheral zone thickness, peripheral zone index, prostatic urethra thickness, the angle and distance of distal prostatic urethra with regard to coronal plane and sagittal plane and so on.ResultsIntravesical prostatic protrusion volume, intravesical prostatic protrusion thickness and peripheral zone volume of prostate volume >80 mL group were significantly higher than these in prostate volume <80 mL group (P<0.001, 0.01, 0.01, respectively). These parameters significantly increased with age (P<0.001, 0.01, 0.05, respectively). Peripheral zone index was significantly lower of prostate volume >80 mL group than these in prostate volume <80 mL group (P<0.05). Peripheral zone index significantly decreased with age (P<0.01). Intravesical prostatic protrusion index had no significant difference in all age groups. Peripheral zone thickness and prostatic urethra thickness had no significant difference in all groups. The distance and angle of distal prostatic urethra prostatic urethra with regard to coronal plane were significantly higher than these with regard to sagittal plane (both P<0.001).ConclusionsThe rearward slope of the prostatic urethra is greater than the left or right offset during the process of benign prostatic hyperplasia. Three-dimensional measurement provides good supports for further clinical and scientific research.

Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

Dataset Information

Role of CYP17 rs743572 Polymorphism in Benign Prostatic Hyperplasia: A Multivariate Integrated Analysis.

Publications

Role of CYP17 rs743572 Polymorphism in Benign Prostatic Hyperplasia: A Multivariate Integrated Analysis.

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