Glutathione S-transferase Gene Variants and Risk of BenignProstate Hyperplasia in a North Indian Population

Abstract

Glutagthione S-transferase (GST) is over-expressed in benign prostate hyperplasia (BPH) patients, but thesignificance of GST polymorphisms for susceptibility to diseases of the prostate is unclear. The objectives ofthis study were to determine relationships between polymorphisms in the GSTM1, T1 and P1 genes with risk ofsymptomatic BPH and influence on standard therapy. A gene polymorphism association study conducted with 160symptomatic 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 (Americanurological association) score >7 and PVR volume ≤200 ml. Patients were treated with α-adrenergic blockersand 5α-reductase inhibitors for 6 months and subdivided based on their significant improvement in parametersbetween pre and post 6 month combined therapy to study associations with the GST polymorphisms. The GSTT1and GSTM1 variants genotyped with multiplex-PCR, whereas GSTP1 polymorphisms were determined withPCR-RFLP (polymerase chain reaction- restriction fragment length polymorphism). We observed a lack ofany 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 symptomaticBPH (p= 0.009, OR= 8.31 95%CI=1.71-40.37). Polymorphisms of GST genes were not associated with respondersor non-responders. Thus the GSTM1 deletion polymorphism is significantly associated with increased risk ofsymptomatic BPH, but none of the genes appearedto influence response to standard BPH therapy.