title: SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, Xinhua Hospital, Medical School of Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gu
authors.forename: Rong
authors.initials: R
authors.lastname: Na
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Sha
authors.initials: S
authors.lastname: Tao
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.forename: Siqun
authors.initials: S
authors.lastname: Zheng
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.forename: Jielin
authors.initials: J
authors.lastname: Sun
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D002681:China; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009929:Organ Size; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000235:genetics*; D011788:Quality of Life
chemical_list: D058891:5-alpha Reductase Inhibitors; D000317:Adrenergic alpha-Antagonists; D008565:Membrane Proteins; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human; C548468:SRD5A2 protein, human
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