Impact of CYP3A4*22 Genetic Variant and Plasma microRNA mir-27b Expression Level on Silodosin Steady-State Concentration and Therapy Outcomes in Patients with Benign Prostatic Hyperplasia: A Prospective Observational Trial
Abstract
Despite the proven efficacy of silodosin for lower urinary tract symptoms (LUTSs), significant interindividual variability in response to pharmacotherapy and the development of adverse events persists. Potential factors for this variability include pharmacogenetic and epigenetic mechanisms regulating drug metabolism.
The aim
. To investigate the impact of CYP3A4*22 polymorphism and circulating microRNA miR-27b level on the pharmacokinetics, efficacy, and safety of silodosin in patients with benign prostatic hyperplasia (BPH).
Materials and methods.
The study included 98 patients with LUTS due to BPH who were prescribed silodosin 8 mg/day for 8 weeks. IPSS and QoL dynamics, and the frequency of adverse events were assessed. The steady-state minimum concentration of silodosin (Css) was determined by HPLC-MS/MS. Genotyping for CYP3A4*22 was performed by real-time PCR. The expression level of plasma miR-27b was determined using RT-qPCR.
Results.
Patients with the CT genotype (12.2%) had significantly higher Css values compared to carriers of the CC genotype (13.44 [6.35; 16.6]
vs
6.15 [3.10; 11.31] ng/mL;
p
= 0.005717). Despite this, the reduction in symptom severity according to IPSS and improvement in QoL were comparable in both groups (
p
>0.05). No correlation was found between Css and IPSS dynamics (
rs
= -0.115554,
p
= 0.257195). MiR-27b levels did not differ between genotypes and did not correlate with either Css or clinical outcomes. The structure of adverse events…
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