Glutathione S-transferase gene variants and risk of benign prostate hyperplasia in a North Indian population.
Glutagthione S-transferase (GST) is over-expressed in benign prostate hyperplasia (BPH) patients, but the significance of GST polymorphisms for susceptibility to diseases of the prostate is unclear. The objectives of this study were to determine relationships between polymorphisms in the GSTM1, T1 and P1 genes with risk of symptomatic BPH and influence on standard therapy. A gene polymorphism association study conducted with 160 symptomatic BPH patients with BPE (benign prostatic enlargement) and LUTS (lower urinary tract symptoms) and 200 age-matched controls. Patient inclusion criteria are age > 50 years prostate size > 30 cm3, AUA (American urological association) score > 7 and PVR volume ≤ 200 ml. Patients were treated with α-adrenergic blockers and 5α-reductase inhibitors for 6 months and subdivided based on their significant improvement in parameters between pre and post 6 month combined therapy to study associations with the GST polymorphisms. 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 the GSTT1 (p=0.45, OR=2.25, 95% CI=1.71-2.22) and GSTP1 (p=0.92 and 0.99) genes. However, there was a significant link with the null alleles of the GSTM1 (p=0.000, OR=2.24, 95%CI=1.46-3.42) gene. The combined analysis of the three genotypes demonstrated further increase in the risk of symptomatic BPH (p= 0.009, OR= 8.31 95%CI=1.71-40.37). Polymorphisms of GST genes were not associated with responders or non-responders. Thus the GSTM1 deletion polymorphism is significantly associated with increased risk of symptomatic BPH, but none of the genes appeared to influence response to standard BPH therapy.
Konwar
Rituraj
R
Endocrinology Division, Central Drug Research Institute, Lucknow, India.
Manchanda
Parmeet Kaur
PK
Chaudhary
Preeti
P
Nayak
V Lakshma
VL
Singh
Vishwajeet
V
Bid
Hemant Kumar
HK
D000368:Aged; D016022:Case-Control Studies; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D012307:Risk Factors; D015996:Survival Rate
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human