Glutathione S-transferase (GST) Gene Variants and risk of BPH (Benign Prostatic Hyperplasia): A report in north Indian population

Abstract

GST is over expressed in BPH patients. Nature of association of GST polymorphism with susceptibility of BPH as a disease different from prostate is limited. The objectives of this study was to determine relationship between polymorphism 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 >30cm3, 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 association of GST polymorphism. 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 lack of association in GSTT1 (p=0.45, OR= 2.25, 95% CI= 1.71-2.22) and GSTP1 (p=0.92 and 0.99) gene. There was a significant association in 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 are not associated with none of the groups of responder and non-responder. GSTM1 deletion polymorphism is significantly associated with the increased risk of symptomatic BPH. None of the GST polymorphism is associated with response of the standard BPH therapy.