Abstract: AIM: To explore the associations between HGPRT activities and genetic polymorphisms and AZA-related adverse reactions in renal transplant recipients so as to provide enough theoretic and experiment evidence for rational use of AZA.METHODS: Erythrocyte HGPRT activity were measured in 86 cases of renal transplant recipients by a modified high-performance liquid chromatography (HPLC) procedure we developed before,genotype of HGPRT IVS6-12C>A was determined by direct sequencing method.Combined with the subject occurrence of adverse reactions,the relationships between HGPRT activity and genetic polymorphisms and AZA-induced adverse reactions were systematically analyzed.RESULTS: HGPRT activity in 86 cases of renal transplant recipients ranged from 44.59 U to 262.16 U and the average activity was (100.17±33.50) U. HGPRT activity in healthy subjects ranged from 28.43 to 153.65 U and the average activity was (99.30±17.21)U. Both of them showed normal distribution.There was no statistically significant difference about HGPRT activity between the renal transplant recipients and the healthy subjects(P>0.05). In the renal transplant recipients, 2 cases of HGPRT-IVS6-12C> A mutation was found and the mutation frequency was 2.30%. No IVS6-12C> A mutation was found in the health subjects. No association was observed between HGPRT activity and genetic polymorphisms(P>0.05).The average HGPRT activity in patients with flu-like symptoms was significantly higher than that in the renal transplant recipients who had no AZA-related adverse reactions[(147.47±101.24) U vs (100.46±29.31) U,P<0.05]. The average HGPRT activities in patients with hematotoxicity, hepatotoxicity and gastrointestinal disturbance were found no significant differences compared with the patients who had no AZA-related adverse reactions (P>0.05). No association was observed between HGPRT genetic polymorphisms and AZA-related adverse reactions(P>0.05).CONCLUSION: In conclusion, before commencing AZA treatment, it is important to measure HPGRT activity in renal transplant recipients and relieve AZA-dose in order to reduce AZA-related flu-like symptoms .

Key words: azathioprine, hypoxanthine guanine phosphoribosyl transferase (HGPRT), adverse drug reaction, enzyme activity, genetic polymorphism