Molecular Analysis of the SRD5A1 and SRD5A2 Genes in Patients with Benign Prostatic Hyperplasia with Regard to Metabolic Parameters and Selected Hormone Levels

Abstract

Introduction: The etiology of benign prostatic hyperplasia (BPH) has not so far been fully explicated. However, it is assumed that changes in the levels of hormones associated with aging can contribute to the development of prostatic hyperplasia. Dihydrotestosterone combines with the androgen receptor (AR) proteins of the prostate gland. Enzyme activity is based on two isoenzymes: type 1 and type 2. 5α-reductase type 1 is encoded by the SRD5A1 gene, and type 2 is encoded by the SRD5A2 gene. The aim of our study was to determine the frequency of the SRD5A1 (rs6884552, rs3797177) and SRD5A2 (rs523349, rs12470143) genes’ polymorphisms, and to assess the relationships between the genotypes of the tested mutations, and the levels of biochemical and hormonal parameters in patients with BPH. Material and Methods: The study involved 299 men with benign prostatic hyperplasia. We determined the serum levels of particular biochemical parameters—fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG)—by the spectrophotometric method, using ready reagent kits. The ELISA method was used to determine the levels of the following hormonal parameters and proteins: total testosterone (TT), free testosterone (FT), insulin (I), luteinizing hormone (LH), and sex hormone binding protein (SHBG). Metabolic syndrome was diagnosed. Genotyping was performed by real-time PCR. Results: We analyzed the relationships between the incidence of particular diseases and the genotypes of the SRD5A1 and SRD5A2 polymorphisms among patients with BPH. The BPH patients with the CC genotype of the SRD5A2 rs523349 and rs12470143 polymorphisms were considerably less frequently diagnosed with metabolic syndrome (MetS) (p = 0.022 and p = 0.023 respectively). Our analysis revealed that homozygotes with the CC of the SDR5A2 rs12470143 polymorphism had visibly higher HDL levels than those with the TT and CT genotypes (p = 0.001). Additionally, we found that the patients with the CC genotype of the SDR5A2 rs12470143 polymorphism had considerably higher FT levels (p = 0.001) than the heterozygotes with the CT and the homozygotes with the TT of the genetic variant analyzed in our study. Furthermore, the patients with at least one G allele of the SRD5A2 rs523349 polymorphism had significantly lower SGBG levels (p = 0.022) compared with the homozygotes with the CC genotype. The presence of at least one A allele (AA + AG genotypes) of the SRD5A1 rs3797177 polymorphism entailed notably lower serum insulin levels than those observed in homozygotes with the GG genotype (p = 0.033). Conclusions: The study described in this article shows that selected SRD5A1 and SRD5A2 polymorphisms can alter the levels of metabolic and hormonal parameters in patients with BPH. Special attention should be paid to the SDR5A2 rs12470143 polymorphism, which is associated with a change in lipid profile, as well as with the inheritance and incidence rate of MetS among these patients. An analysis of the frequency o...

Steroid 5 alpha-reductase 2 enzyme variants, biomass exposure and tobacco use in Mexican patients with prostate cancer

“…Finally, regarding benign prostate diseases, a meta-analysis undertaken in 2017 by Zeng et al ( 85 ) found a risk of developing BPH in individuals carrying the A49T variant (OR=2.75; CI=1.32–5.69), but this was not statistically significance (P=0.373). By contrast, the results of studies concerning the V89L variant and its association with the development of BPH and PSA changes have been contradictory ( 86 , 87 ). A previous study reported that the Val/Leu+Leu/Leu genotype (P=0.047; OR=1.62; CI=1.00–2.61) was associated with the development of this benign condition, but not with the development of PCa ( 88 ).…”

Features of the use of Serenoa repens extracts in the long-term therapy of benign prostatic hyperplasia

“…Постоянная стимуляция андрогеновых рецепторов при прогрессии ДГПЖ необходима для роста и функции ткани ПЖ, путем трансактивации домена, который закодирован в первом экзоне гена АР (Xq 11-12) [25][26][27]. При исследовании полиморфизма генов, кодирующих 5α-редуктазу 2 типа (SRD 5A1 и SRD 5 A2), было установлено, что имеется тесная взаимосвязь между выраженностью полиморфизма генов, объемом ДГПЖ, эффективностью проводимой антиандрогенной терапии и концентрацией половых гормонов и их метаболитов [28,29]. Известно, что α 1 -адренорецепторы непосредственно принимают участие в процессе действия внутриклеточных эффекторов, которые влияют на объем и тонус гладкомышечных элементов ПЖ, что объясняет явный результат их активации [30].…”

Serenoa repens extracts: In vitro study of the 5α-reductase activity in a co-culture model for Benign Prostatic Hyperplasia

“…Serenoa repens extracts: In vitro study of the 5α-reductase activity in a co-culture model for Benign Prostatic Hyperplasia action of enzyme 5α-reductase, which leads to an increase of the prostate size and causes various disorders, especially in the lower urinary tract (1,2). The approach for the treatment and therapy of BPH is mainly based on the use of inhibitors of 5α-reductase enzyme, in particular natural inhibitors, such as the active compounds present in the alcoholic extracts deriving from species Serenoa repens, a typical palm common in the Subtropical sandy soils and in the southern coasts of the United States.…”

“…Benign Prostatic Hyperplasia (BPH) is a form of benign tumor that occurs in humans mainly with ageing. In fact, it affects more than 50% of over 50 years old males, with an incidence rate directly proportional to age (1). It is characterized by an increased synthesis of dihydrotestosterone (DHT) starting from testosterone, due to the several EU Member States (including Italy) and belonging to the class of drugs employed to counter the increase in prostatic volume in males with BPH, have been tested.…”