Glutathione S-transferase M1 gene polymorphism is associated with susceptibility to impaired long-term allograft outcomes in renal transplant recipients.
BACKGROUND
Despite improved post-transplantation care, progress in long-term kidney allograft survival of diabetic renal transplant recipients (pre-DM RTR) is worse than that of non-diabetic recipients (non-DM). We hypothesized that there are other potential risk factors, that predispose RTR to adverse renal allograft outcomes.


METHODS
A total of 323 transplant recipients who underwent renal transplantation between March 2000 and January 2008 were recruited. The composite end-point consisted of serum creatinine (SCr) doubling, graft failure, and death. Baseline clinical data were recorded, and polymerase chain reaction-restriction fragment length polymorphism measurements of interleukin (IL)-4, IL-10, IL-23, glutathione S-transferase (GST)A1, GSTM1, and GSTP1 polymorphisms were determined. The risk factors for developing the primary outcome were analyzed among these clinical and genetic factors.


RESULTS
Within a mean follow-up of 71.1 ± 24 months, there were 43 (13.3 %) patients with the primary outcome. Stepwise multivariate Cox regression analysis was used to determine the risk factors for the primary outcome of RTR. Renal transplant recipients who possessed the GSTM1 null genotype had a 2.2-fold risk (95 % CI: 1.10-4.40; P = 0.026) of developing the primary outcome. Additionally, RTR that had DM before transplantation (aHR: 3.31; 95 % CI: 1.77-6.20; P = 0.0002) or changes in SCr 6 to 12 months after transplantation (aHR: 2.83; 95 % CI: 1.29-6.19; P = 0.0095) had an increased risk of developing the primary outcome.


CONCLUSIONS
In addition to the adverse role played by DM, the GSTM1 null genotype also has an unfavorable influence on the long-term allograft outcome of RTR.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Horng-Rong
HR
Chang
Jen-Pi
JP
Tsai
Shun-Fa
SF
Yang
Chih-Kuang
CK
Lin
Jong-Da
JD
Lian
D000328:Adult; D054458:Amplified Fragment Length Polymorphism Analysis; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D005500:Follow-Up Studies; D005819:Genetic Markers; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006085:Graft Survival; D006801:Humans; D007378:Interleukins / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000401:mortality / Q000601:surgery*; D016030:Kidney Transplantation / Q000401:mortality; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure
D015415:Biomarkers; D003404:Creatinine; D005819:Genetic Markers; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007378:Interleukins; C484555:GSTA1 protein, human; C496556:GSTP1 protein, human