Renal transplantation
Rejection: Diagnosis
Uridine Diphosphate Glucuronosyltransferase 2B7 Variant p.His268Tyr as a Predictor of Kidney Allograft Early Acute Rejection

https://doi.org/10.1016/j.transproceed.2013.01.010Get rights and content

Abstract

Background

Uridine diphosphate glucuronosyltransferase (UGT2B7) is responsible for conversion of mycophenolic acid to mycophenolic acyl-glucuronide (acylMPAG). Conflicting data exist regarding the role of UGT2B7 p.His268Tyr (802C>T, rs7439366) variant in the clinical course following organ transplantation.

Study Aim

The aim of this study was to reveal an association between UGT2B7 p.His268Tyr (802C>T, rs7439366) polymorphism and kidney transplantation outcome.

Study Design, Patients, and Method

Genomic DNA of 235 kidney transplant recipients was genotyped for UGT2B7 802C>T using TagMan single nucleotide polymorphism (SNP) genotyping assay. Maintenance immunosuppression used mycophenolate mofetil (MMF) and cyclosporine A (n = 137) or tacrolimus (n = 98). Primary end-point was biopsy-confirmed acute rejection within 3 and 12 post-transplantation months. Secondary end-points included gastrointestinal side effects, leukopenia, lymphopenia, neutropenia, and infections. Statistical analysis was performed with the aid of SAS System using kernel-smoothed estimates of acute graft rejection hazard function. The log-rank test and hazard ratio were used to reflect association between UGT2B7 802C>T variant and risk of acute graft rejection.

Results

Within 3 postimplantation months 38 (16.2%) patients experienced acute rejection; 33 were allele C carriers in UGT2B7 802C>T SNP and 5 were TT homozygotes (P < .0457). Allele C–associated risk of rejection was 2.50 and remained between 2.19 and 3.02 after adjustment for clinical confounders, ie, HLA mismatch, panel-reactive antibodies, donor age, repeated transplantation, induction therapy, donor type, delayed graft function, applied calcineurin inhibitor, or MMF dosing. We found no association between the polymorphism and gastrointestinal side effects, leukopenia, lymphopenia, neutropenia, and infections.

Conclusion

UGT2B7 802C>T genotyping may help identify patients with excessive early acute rejection risk.

Section snippets

Patients and Methods

The study was approved by the local Ethics Committee at the Medical University of Warsaw and was conducted according to the approved protocols.

The prospective, historical cohort study of kidney transplant recipients included 235 patients who fulfilled the following criteria: given informed consent, availability of DNA sample, access to standard medical file, triple maintenance immunosuppression based on glucocoticosteroids, and MMF and either cyclosporine A or tacrolimus given from the day of

Results

The overall characteristics of the study population and the frequencies of UGT2B7 802C>T genotypes are given in Table 1. The observed distribution of CC, CT, and TT genotypes was consistent with the Hardy-Weinberg equilibrium (P = .22; χ2 = 1.49). On the crude analysis the presence of UGT2B7 802C>T allelic variants was insignificant for acute rejection risk, the incidence of myelosupression (leukopenia, granulocytopenia, lymphopenia, and thrombocytopenia), GI side effects, and infectious

Discussion

Our results show that in kidney transplant recipients the association between UGT2B7 802C>T polymorphism and acute rejection is limited to the early post-transplantation weeks. This observation confirms the results in stable thoracic organ recipients.1 Other authors who did not find such a relationship were analyzing a clinical course of kidney recipient populations over a period of 12 post-transplantation months.3, 4

UGT2B7 was identified as one of the major uridine

References (15)

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This study was supported by grants from the Polish Ministry of Science and Higher Education N N402 4266 33 and Medical University of Warsaw 1M15/N/2010-2012.

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