Glutathione S-transferase (GST) gene variants and risk of benign prostatic hyperplasia: a report in a North Indian population

Asian Pac J Cancer Prev. 2010;11(4):1067-72.

Abstract

Glutathione S-transferases may be over expressed in benign prostate hyperplasia (BPH) but association of GST polymorphism with susceptibility to the disease is unclear. The objective of this study was to determine relationships between polymorphisms in the GSTM1, T1 and P1 genes with risk of symptomatic BPH and response to standard therapy. The study population comprised 160 symptomatic BPH patients with BPE (benign prostatic enlargement) and LUTS (lower urinary tract symptoms) and 200 age-matched controls. Patient inclusion criteria were: age>50 years; prostate size>30 cm3; AUA (American Urological Association) score>7; and PVR volume≤200 ml. Patients were treated with alpha-adrenergic blockers and 5alpha-reductase inhibitors for 6 months and subdivided based on significant improvement in parameters between pre and post combined therapy. The GSTT1 and GSTM1 variants genotyped with multiplex-PCR, whereas GSTP1 polymorphisms were determined with PCR-RFLP (polymerase chain reaction- restriction fragment length polymorphism). We observed a lack of any association with GSTT1 (p=0.45, OR=2.25, 95% CI=1.71-2.22) and GSTP1 (p=0.92 and 0.99) genes. There was a significant positive association with null alleles of the GSTM1 (p=0.000, OR=2.24, 95%CI =1.46-3.42) gene. Combined analysis of the three genotypes demonstrated further increase in the risk of symptomatic BPH (p=0.009, OR=8.31 95%CI=1.71-40.4). Polymorphisms of GST genes were not associated with rates for responders and non-responders. GSTM1 deletion is significantly associated with the increased risk of symptomatic BPH, but none of the GST polymorphisms appears associated with response to standard BPH therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-alpha Reductase Inhibitors / therapeutic use
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use
  • Aged
  • Azasteroids / therapeutic use
  • Dutasteride
  • Genetic Predisposition to Disease
  • Genotype
  • Glutathione S-Transferase pi / genetics*
  • Glutathione Transferase / genetics*
  • Humans
  • India / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Prostatic Hyperplasia / drug therapy
  • Prostatic Hyperplasia / epidemiology
  • Prostatic Hyperplasia / genetics*
  • Sulfonamides / therapeutic use
  • Tamsulosin
  • Treatment Outcome

Substances

  • 5-alpha Reductase Inhibitors
  • Adrenergic alpha-1 Receptor Antagonists
  • Azasteroids
  • Sulfonamides
  • glutathione S-transferase T1
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Tamsulosin
  • Dutasteride