P284
INOSINE MONOPHOSPHATE DEHYDROGENASE (IMPDH) POLYMORPHISMS AND
GRAFT OUTCOME IN RENAL TRANSPLANTATION
Shah, S1, Harwood, S1, Döhler, B2, Opelz, G2, Yaqoob, M1
1
Department of Translational Medicine and Therapeutics, Barts and the London School of
Medicine and Dentistry, London, 2Department of Transplantation Immunology, University of
Heidelberg, Heidelberg, Germany
Inosine monophosphate dehydrogenase (IMPDH), the target enzyme for mycophenolate mofetil
(MMF), displays wide inter-individual variability in enzyme activity which may in part be genetically
determined. Presence of the T allele in IMPDH I polymorphism 9197C>T (rs2278293) was shown to
be associated with reduced risk of acute rejection, whereas the G allele in the IMPDH II 3757A>G
polymorphism (rs11706052) was shown to confer an increased risk. The aim of this study was to
investigate in a large cohort of patients the influence of these polymorphisms on long-term graft and
patient survival.
A random sample of 1040 recipients from the Collaborative Transplant Study DNA bank was
genotyped for the variants 9197C>T IMPDH I and 3757A>G IMPDH II. Compared to the AA
genotype of IMPDH I, patients carrying the T allele (AT or TT) had similar death censored graft
survival, patient survival, rejection rates, post-transplant serum creatinine and tolerated comparable
MMF doses at 1 year. Carriage of the G allele (AG or GG) compared to the AA genotype of IMPDH
II did not increase the risk of rejection, graft dysfunction, or impaired graft or patient survival, and
there was no association between MMF dose tolerated at 1 year and genotype.
This study does not support previous evidence for an association between these IMPDH variants and
renal allograft rejection. Furthermore we suggest that these two SNPs are not associated with MMF
dose after renal transplantation. In our opinion, the currently available evidence does not support
routine screening of patients for these SNPs. The search for polymorphisms in the IMPDH gene in
order to guide MMF therapy for optimizing outcome and minimizing toxicity continues.