Résumé
The inhibition of 5-α reductase type 2 (SRD5A2) by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement (BPE). Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy. Our previous work showed that methylated cytosine-phosphate-guanine (CpG) islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression. Here, we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein (scored 0-100) occurred in 10.0% (4/40) of benign adult prostates. We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1 (DNMT1) expression. In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment, and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2'-deoxycytidine (5-Aza-CdR) or N-phthalyl-L-tryptophan (RG108). Furthermore, we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis. Ten methylated CpG dinucleotides, including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon, were found in a CpG island located from -400 bp to +600 bp in SRD5A2, which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression. Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2, which may partially account for the resistance to finasteride observed in certain BPE patients.
Résumé
Background: To evaluate the correlation of Visual Prostate Symptom Score (VPSS) with International Prostate Symptom Score (IPSS) and Maximum Urinary Flow (Qmax). To investigate the effect of educational level on the ability to independently complete the VPSS versus the IPSS and time taken to do so.Methods: Bio data was taken from men with lower urinary tract symptoms (LUTS) due to Benign Prostatic Enlargement (BPE) who presented at the Urology clinic of Jos University Teaching Hospital. They were administered the IPSS questionnaire and VPSS pictogram, which they completed with or without physician assistance and the time taken to do so was noted. They subsequently had uroflowmetry done on same visit and the data was recorded in a structured proforma. Statistical analysis was done using SPSS(R) version 20. Correlation test was done for VPSS, IPSS and Qmax while the paired t-test was used for the average time spent in completing both questionnaires. A p-value <0.05 was considered as significant.Results: Eighty-five men (aged 42 to 94 years) were enrolled in the study. The VPSS correlated significantly with the IPSS in terms of total score (r = +0.684, p<0.001) and QoL (r = +0.570, p<0.001), as well as with the Qmax (r = -0.222, p = 0.041). A greater proportion (21.2%) of men with limited education could complete the VPSS without physician assistance as compared to the IPSS (6.0%) and the average time taken to complete the VPSS (170.51 seconds) was significantly shorter than the time taken to complete the IPSS (406.42 seconds).Conclusions: The VPSS correlates significantly with the IPSS and Qmax. It can be completed without physician assistance by a greater proportion of men with limited education within a shorter time period.