SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists

J Urol. 2013 Aug;190(2):615-9. doi: 10.1016/j.juro.2013.03.024. Epub 2013 Mar 14.

Abstract

Purpose: Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population.

Materials and methods: We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment.

Results: The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively).

Conclusions: SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.

Keywords: (TA)(n) repeat; 3′-UTR; 3′-untranslated region; 5α-dihydrotestosterone; BPH; DHT; Homo sapiens steroid-5-α-reductase, α polypeptide 1; Homo sapiens steroid-5-α-reductase, α polypeptide 2; PSA; SNP; SRD5A1; SRD5A1 protein, human; SRD5A2; SRD5A2 protein, human; TPV; benign prostatic hyperplasia; fPSA; free PSA; polymorphism, single nucleotide; prostate; prostate specific antigen; prostatic hyperplasia; single nucleotide polymorphism; tPSA; tSNP; tagging SNP; thymine-adenine di-nucleotide repeat; total PSA; total prostate volume.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics*
  • 5-alpha Reductase Inhibitors / therapeutic use*
  • Adrenergic alpha-Antagonists / therapeutic use*
  • China
  • Disease Progression
  • Genotype
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Organ Size
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Prostatic Hyperplasia / drug therapy*
  • Prostatic Hyperplasia / genetics*
  • Quality of Life

Substances

  • 5-alpha Reductase Inhibitors
  • Adrenergic alpha-Antagonists
  • Membrane Proteins
  • 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
  • SRD5A1 protein, human
  • SRD5A2 protein, human