TPMT Genetic Polymorphism And Its Clinical Implication In Renal Transplant Recipients With Azathioprine Treatment

Objective: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzes theS-methylation of thiopurine drugs. TPMT activity exhibits an interindividualvariability, mainly as a result of genetic polymorphism in the coding regions of theTPMT gene. It has previously been reported that 4 variant alleles: TPMT*2, *3A, *3Band *3C are responsible for over 80%~95% cases of low or intermediate TPMTactivity. Several foreign studies showed that the toxicity and therapeutic efficacy ofthiopurine drugs were influenced by TPMT polymorphism. However, there are nosystemic study on the frequencies of TPMT alleles and the impact of TPMT genotypeon individualized therapy in Chinese renal transplant patients. The purpose of thisstudy was to explore the association between TPMT polymorphisms and the immuneinhibition effects/toxicity of azathioprine in renal transplant recipients undergoingtriple immunosuppressive therapy including azathioprine, cyclosporine, andprednisone.Patients and methods1 Patients and biochemical/clinical data collectionOne hundred and ninety-three patients underwent renal transplantation betweenJanuary 1998 and December 2003. Seventy-one of 193 patients were excluded fromevaluation. Finally, 122 patients (32 females, 90 males) with a mean age of 39.2 ± 9.9years (range 17- 69 years) and a mean weight of 64.5 ± 8.0kg (range 43.0- 81.5 kg)...