INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: 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. METHODS: 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. RESULTS: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. CONCLUSION: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.
Authors: Jamison Chang; Jennie Z Ma; Qing Zeng; Sylvia Cechova; Adam Gantz; Caroline Nievergelt; Daniel O'Connor; Michael Lipkowitz; Thu H Le Journal: Am J Physiol Renal Physiol Date: 2012-12-05
Authors: B E Gutiérrez-Amavizca; R Orozco-Castellanos; R Ortíz-Orozco; J Padilla-Gutiérrez; Y Valle; N Gutiérrez-Gutiérrez; G García-García; M Gallegos-Arreola; L E Figuera Journal: Indian J Nephrol Date: 2013-11
Authors: Bin Yang; Nicolas Sylvius; Jinli Luo; Cheng Yang; Zhanyun Da; Charlottelrm Crotty; Michael L Nicholson Journal: Front Immunol Date: 2021-07-01 Impact factor: 7.561