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  • Title: [Association between metabolic enzyme genotype of azathioprine and drug tolerance in patients with rheumatic diseases].
    Author: Zhan ZP, Liang LQ, Yang XY, Wang YX, Huang M, Li H.
    Journal: Zhonghua Yi Xue Za Zhi; 2007 Jul 03; 87(25):1734-7. PubMed ID: 17919375.
    Abstract:
    OBJECTIVE: To discuss the relationship between the genotype of thiopurine methyltransferase (TPMT) and azathioprine tolerance in the 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. The 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, 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 had used azathioprine, and bone marrow suppression occurred within 1 month of using the drug, including 2 cases of severe crisis of hematopoietic system. CONCLUSION: Patients with mutation alleles of TPMT are intolerant to azathioprine, and likely to have severe crisis of hematopoietic system. To detect the TPMT genotype before using azathioprine is significant to improve the therapeutic safety.
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