Abstract: 【Objective】 To discuss the relationship between the genotype of thiopurinemethyltransferase (TPMT) and azathioprine(AZA) tolerance in the patients with demyelinating diseases in the central nervous system (CNS). 【Methods】 Mutation alleles of TPMT in 224 patients included 135 demyelinating diseases in CNS and 89 non-demyelinating diseases in CNS were detected by polymerase chain reaction (PCR)-SNaPshot. TPMT mutation rate between demyelinating diseases and non-demyelinating diseases and the incidence of adverse drug reactions between TPMT mutation and non-mutation group with AZA were compared by χ2. 130 patients with demyelinating diseases were treated with AZA (25-100 mg/d) and finished 2 months’ follow-up. 【Results】 In 224 patients

9 cases of heterozygote of TPMT *3C were detected including 5 demyelinating diseases and 4 non-demyelinating diseases

but no mutation of TPMT *2

*3A or TPMT *3B was found. The difference of TPMT mutation rate between demyelinating diseases and non-demyelinating diseases was not significant. Patients in TPMT mutation group all had adverse drug reactions after AZA treatment

while the incidence of adverse drug reactions in non-mutation group was 8.8%. In 130 patients who used AZA

11 of which suffered impaired liver function

4 of which were complicated with hematopoietic system and 1 of which had impaired liver function and hematopoietic system. And 4 patients suffered impaired liver function

1 patient suffered hematopoietic system in 5 cases of heterozygote of TPMT *3C. 【Conclusions】 The demyelinating patients with TPMT mutation had high side-effective risk when they used AZA. To detect the TPMT genotype before using AZA is significant to improve the therapeutic safety.