LAUSR

The pharmacokinetics and pharmacodynamics of the immunosuppressive drug mycophenolate mofetil (MMF) are subject to significant interindividual variability that affects its efficacy and toxicity. The present study focused on the genetic factors potentially involved in the variability of the response to this drug in kidney transplantation, while taking into account the influence of non-genetic factors. 276 kidney transplant patients treated with MMF were involved, recruited from the Nephrology and transplantion Department of Sahloul Hospital. Data on transplantation, exposure to MMF and clinical outcomes of the patients were collected. A PCR-RFLP genetic study of 9 polymorphisms of UGT, SLCO and IMPDH was performed. Were studied the relationship between the genetic polymorphisms and the exposure to MMF, the risk of acute and chronic rejection of the kidney graft, as well as the adverse effects of MMF. This study showed that the variant alleles of polymorphisms UGT1A9 -2152C>T and IMPDH II 3757T>C would increase the risk of acute and chronic rejection. The variant allele of SLCO1B1 388A>G would protect against acute rejection. The variant allele of the UGT1A9 98T>C polymorphism would increase the risk of diarrhea, unlike the variant allele of the UGT1A9 -275T>A polymorphism, which appears to be a protective factor against diarrhea. The variant allele of the UGT1A8 518C>G polymorphism would increase the risk of infections. However, relationship between genetic polymorphisms and exposure to MMF was not demonstrated. These results highlight the need to take genetic variability into account in predicting the therapeutic response to MMF before initiating the treatment. Acute rejection and genetic polymorphisms SNP Genotype Acute rejection