Role of TPMT Genetic Polymorphism in the Individualized Treatment of Thiopurine Drug / 现代检验医学杂志

Thiopurine S-methyltransferase (TPMT) is an important and key cytoplasmic enzyme in the metabolism of thiopurine drugs,whose activity can directly determine the amount of thiopurine drugs metabolized to cytotoxic 6-thioguanine nucleotides and consequently influence clinical efficacy and adverse drug reactions of thiopurine drugs.In order to deepen knowledge and role of genetic polymorphism of tpmt in the individualized thiopurine drug treatment,this present review mainly covered the following three frequently concerned aspects,including i) whether or not to determine the activity of TPMT priot to treatment of thiopurine drugs;ii) to genotype or to phenotype;iii) how to choose genotype methods.

Evaluation of thiopurine methyltransferase genotyping and enzyme activity detection in treatment of patients with inflammatory bowel disease / 中华消化杂志

Objective To assess the predictive value of thiopurine methyltransferase genotyping and enzyme activity in relation to side effects in patients with inflammatory bowel disease (IBD) who were treated with azathioprine (AZA). Methods One hundred and eleven IBD patients (26 with ulcerative colitis and 86 with Cronh's disease) with indication of AZA administration between April 2004 and Dec. 2009 were enrolled. All patients received 2 mg/kg of AZA daily. Polymerase chain reaction and high performance liquid chromatography were used to genotype the TPMT * 2, * 3A, * 3B, * 3C and to detect TPMT activity, respectively. The association of TPMT genotype and activity with side effects was analyzed in patients treated with AZA for 24 weeks or more, or in those discontinued AZA because of adverse effects. Results Adverse effects were reported in 38(33. 9%) patients, the most frequent being myelosuppression (20. 5%). The frequency of TPMT * 3C heterozygous mutation was 0. 9% (1/112). The TPMT activity was (12. 9±4. 8) U/ml RBC with unimodal distribution. One patient with TPMT * 3C heterozygous mutation developed myelosuppression at the 4th week after AZA treatment. The TPMP genotype myelosuppression patients. Conclusions TPMT genotype mutation and low enzyme activity can be used to predict myelosuppression with high specifically and low sensitivity. In patients treated with AZA, co-administration of 5-ASA results in a high frequency of myelosuppression with no effect on TPMT activity.