The pharmacogenetics of mycophenolate mofetil in Tunisian renal transplant patients.

Abstract

Aim: The effects of variants in IMPDH, UGT1A9, UGT1A8, UGT2B7 and SLCO1B1 genes on the efficacy and safety of mycophenolate mofetil (MMF) in the Tunisian population were investigated. Materials & methods: A total of245 kidney transplant patients being treated with MMF wererecruited and cotreated with cyclosporine or tacrolimus. Genotyping was performed using thepolymerase chain reaction-restriction fragment length polymorphismmethod. MMF, cyclosporine and tacrolimus trough levels were measured by immunoassay. The AUC (AUC0-12hMPA) was estimated by a Bayesian method. Results: In the tacrolimus-treated group, anemia and diarrhea were associated with the UGT1A9-98C and UGT1A9-275T alleles, respectively (p<0.05). In the cyclosporine-treated group, leukopenia was associated with theSLCO1B1-521T allele (p<0.05). Both groups had an increased risk of rejection (p<0.05) associated with the variant alleles of IMPDH2-3757T>C, UGT1A9-2152C>T and UGT1A9-275C>A and the common allele of SLCO1B1-388A>G. However, no significant association was foundbetween the studied genotypes and AUC0-12hMPA or cotreatment levels. Conclusion: The results constitute preliminary evidence for the inclusion of the pharmacogenetics of MMF in kidney pretransplantation evaluations.