Evaluation of thiopurine methyltransferase genotyping and enzyme activity detection in treatment of patients with inflammatory bowel disease
10.3760/cma.j.issn.0254-1432.2010.07.002
- VernacularTitle:硫嘌呤甲基转移酶基因型和酶活性检测在炎症性肠病治疗中的临床价值
- Author:
Fangbin ZHANG
;
Liang DING
;
Xiang GAO
;
Hui LIU
;
Yinglian XIAO
;
Minhu CHEN
;
Min HUANG
;
Pinjin HU
- Publication Type:Journal Article
- Keywords:
Thiopurine drugs;
Thiopurine methyltransferase;
Inflammatory bowel disease
- From:
Chinese Journal of Digestion
2010;30(7):436-440
- CountryChina
- Language:Chinese
-
Abstract:
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.
