Thiopurine S-methyltransferase Polymorphisms and the Relationship between the Mutant Alleles and the Adverse Effects in Systemic Lupus Erythematosus Patients Taking Azathioprine / 대한류마티스학회지

ABSTRACT

OBJECTIVES: To elucidate the genetic basis for Thiopurine methyltransferase (TPMT) polymorphism and investigate the relationship between TPMT mutant and the adverse effect in patients with systemic lupus erythematosis (SLE) taking azathioprine (AZA) in Korea. METHODS: The TPMT genotype was determined in two hundred healthy adults and 342 patients with SLE by MALDI-TOF and correlated with the effects of clinical exposure to AZA. RESUTLS TPMT polymorphism were detected in 2/200 healthy adults (1%), which were heterozygotes with TPMT*3C and TPMT*6 allele, respectively, and 17/342 (4.97%), which were 12 heterozygotes with TPMT*3C and 5 heterozygotes with TPMT*6 allele, respectively, which had a higher frequency of TPMT mutant alleles compared to the healthy controls (p=0.015). Severe nausea occurred in 4 patient with TPMT*3C allele, and severe bone marrow toxicity in a patient with TPMT*6 allele taking AZA. Twenty three in 94 (24.47%) SLE patients taking AZA were suspicious of the adverse effects such as leucopenia (n=17), nausea (n=4) and abnormal liver function test (n=1). AZA was relatively well tolerated among the rest of them. CONCLUSION: The heterozygote with TPMT*3C and *6 were frequently detected in the patient with SLE compared to healthy adults and there was no statistical correlation between TPMT genotype and AZA toxicity. TMPT genotyping cannot replace regular blood monitoring in SLE patients on AZA treatment.