Singh Ranjana, Manchanda Parmeet K, Kesarwani Pravin, Srivastava Aneesh, Mittal Rama D
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India.
Clin Transplant. 2009 Aug-Sep;23(4):490-8. doi: 10.1111/j.1399-0012.2009.00985.x. Epub 2009 Apr 17.
Glutathione S-transferases (GSTs) are important in protection against xenobiotic compounds and toxicity caused by immunosuppressants in renal transplant recipients. In the present study we hypothesize that genetic variability in GSTM1, GSTM3, GSTP1 and GSTT1 genes may be associated with allograft outcome.
The study included 223 controls and 273 transplant recipients categorized into 184 stable graft function (SGF), 57 rejection episodes (RE) and 32 delayed graft function (DGF). The polymorphism was studied using multiplex PCR and PCR-RFLP.
GSTM1 null genotype showed a 3.35-fold higher risk for rejection in SGF vs. RE category [95% confidence interval (CI) 1.27-8.84, p = 0.014]. Mutant (G) allele of GSTP1 was associated with a 5.52-fold risk for DGF (95% CI 1.37-22.17, p = 0.016). Kaplan-Meier analysis revealed significantly lower mean time to first RE in null genotype as compared with GSTM1 present patients (Log p = 0.002). The dose adjusted C(2) levels in null genotype was higher as compared with GSTM1 present patients at one (p = 0.007) and three months (p = 0.027) post transplantation.
Patients with variant genotype of GSTM1 and GSTP1 were at higher risk for rejection and delayed functioning of the allograft, respectively, supporting the hypothesis for involvement of GST isoform variants in allograft outcome in renal transplant recipients.
谷胱甘肽S-转移酶（GSTs）对于保护肾移植受者免受外源性化合物和免疫抑制剂所致毒性作用具有重要意义。在本研究中，我们假设GSTM1、GSTM3、GSTP1和GSTT1基因的遗传变异性可能与移植肾结局相关。
该研究纳入了223名对照者和273名移植受者，后者被分为184例移植肾功能稳定（SGF）者、57例发生排斥反应（RE）者和32例移植肾功能延迟恢复（DGF）者。采用多重PCR和PCR-RFLP技术研究基因多态性。
在SGF组与RE组中，GSTM1基因缺失型基因型发生排斥反应的风险比为3.35倍[95%置信区间（CI）1.27 - 8.84，p = 0.014]。GSTP1基因的突变型（G）等位基因与发生DGF的风险比为5.52倍（95% CI 1.37 - 22.17，p = 0.016）。Kaplan-Meier分析显示，与GSTM1基因存在的患者相比，基因缺失型患者首次发生RE的平均时间显著缩短（对数p = 0.002）。在移植后1个月（p = 0.007）和3个月（p = 0.027）时，基因缺失型患者经剂量调整后的C(2)水平高于GSTM1基因存在的患者。
GSTM1和GSTP1基因变异型基因型的患者分别发生移植肾排斥反应和移植肾功能延迟恢复的风险更高，这支持了GST同工酶变异体参与肾移植受者移植肾结局的假设。
