Presentation: Association between Metabolic Enzyme Genotype of Azathioprine and Drug Tolerance in Patients with Rheumatic Diseases (2007)

845 Association between Metabolic Enzyme Genotype of Azathioprine and Drug Tolerance in Patients with Rheumatic Diseases

PURPOSE :To discuss the relationship between genotype of thiopurine methyltransferase(TPMT) and azathioprine tolerance in patients with rheumatic diseases. METHODS: Four common mutation alleles of TPMT in 200 patients with rheumatic diseases [TPMT*2(G238C), TPMT*3A(A719G/G460A), TPMT*3B(G460A), TPMT*3C(A719G)] were detected by allele specific polymerase chain reaction (AS-PCR) and polymerase chain reaction -restriction fragment length polymorphism (PCR-PFLP). 194 patients who had used azathioprine finished the 3 months’ follow-up. RESULTS: In the 200 patients with rheumatic diseases, 4 cases of heterozygote of TPMT*3C were detected , but no mutation of TPMT*2, TPMT*3B or TPMT*3A was found. Genotypic frequency of wild-type homozygote was 98%, and that of heterozygote (TPMT*1/TPMT*3C) was 2%. Mutation allele frequency in these patients was 1%. Average of TPMT activity of the 4 cases of heterozygote was (2.4±1.2)U/ml red blood cells (U/ml RBC), significantly lower than that of the 196 cases of homozygote which was (12.2±6.8)U/ml RBC. In the 194 patients who had used azathioprine, bone marrow suppression occurred in 18 patients, 2 of which suffered severe crisis of hematopoietic system, and 6 of which were complicated with impaired liver function. In the 4 patients with heterozygote, 3 of which had used azathioprine, bone marrow suppression occurred within 1 month of using the drug, including 2 cases of severe crisis of hematopoietic system. CONCLUSIONS :Patients with mutation alleles of TPMT are intolerant to azathioprine, likely to have severe crisis of hematopoietic system. To detect TPMT genotype before using azathioprine is significant to improve the therapeutic safety.

  Z. Zhan, doctor, 3; X. Yang, doctor, 3; L. Liang, doctor, 3; Y. Wang, Teacher, 3; M. Huang, professor, 3.