Konwar Rituraj, Manchanda Parmeet Kaur, Chaudhary Preeti, Nayak V Lakshma, Singh Vishwajeet, Bid Hemant Kumar
Endocrinology Division, Central Drug Research Institute (CDRI), India.
Asian Pac J Cancer Prev. 2010;11(4):1067-72.
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.
谷胱甘肽S-转移酶在良性前列腺增生（BPH）中可能过度表达，但GST基因多态性与该疾病易感性之间的关联尚不清楚。本研究的目的是确定GSTM1、T1和P1基因多态性与有症状BPH风险及对标准治疗反应之间的关系。研究人群包括160例有症状的BPH患者，伴有良性前列腺增生（BPE）和下尿路症状（LUTS），以及200例年龄匹配的对照。患者纳入标准为：年龄>50岁；前列腺体积>30 cm³；美国泌尿外科学会（AUA）评分>7；残余尿量（PVR）≤200 ml。患者接受α-肾上腺素能阻滞剂和5α-还原酶抑制剂治疗6个月，并根据联合治疗前后参数的显著改善进行细分。采用多重聚合酶链反应（multiplex-PCR）对GSTT1和GSTM1变体进行基因分型，而GSTP1基因多态性则通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）进行测定。我们观察到GSTT1（p=0.45，比值比[OR]=2.25，95%置信区间[CI]=1.71-2.22）和GSTP1（p=0.92和0.99）基因与疾病无任何关联。GSTM1基因的无效等位基因存在显著正相关（p=0.000，OR=2.24，95%CI =1.46-3.42）。对三种基因型的联合分析表明，有症状BPH的风险进一步增加（p=0.009，OR=8.31，95%CI=1.71-40.4）。GST基因多态性与治疗反应者和无反应者的比例无关。GSTM1基因缺失与有症状BPH风险增加显著相关，但GST基因多态性均未显示与BPH标准治疗的反应相关。
