Influence of genetic polymorphisms in GSTM1, GSTM3, GSTT1 and GSTP1 on allograft outcome in renal transplant recipients.
BACKGROUND
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.


CONCLUSIONS
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.
Singh
Ranjana
R
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Uttar Pradesh, India.
Manchanda
Parmeet K
PK
Kesarwani
Pravin
P
Srivastava
Aneesh
A
Mittal
Rama D
RD
D000328:Adult; D016022:Case-Control Studies; D051799:Delayed Graft Function / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D007194:India; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1; C483009:GSTM3 protein, human; C496556:GSTP1 protein, human