Background:Thiopurines are commonly used for the induction and maintenance of remission in patients with inflammatory bowel disease (IBD). However, the toxicity limits its clinical use. Several studies have suggested that activity of thiopurine S-methyltransferase (TPMT) may predict the occurrence of azathioprine (AZA) toxicity. Aims: To investigate the correlation between TPMT activity and genotype and the occurrence of AZA-induced toxicity in the treatment of IBD patients. Methods: Seventy-eight IBD patients from Oct. 2008 to Dec. 2010 at Shanghai Renji Hospital were enrolled. All the patients were treated with AZA 1-1.5 mg/kg daily. TPMT activity was measured by high performance liquid chromatography (HPLC), and TPMT genotype was detected by direct sequencing and PCR. The association of TPMT activity and genotype with AZA toxicity was analyzed. Results: AZA toxicity occurred in 19 patients, including 4 patients experienced bone marrow toxicity (BUT). The median TPMT activity of 78 IBD patients was (36.10±10.11) nmol 6-MTG·gHb-1·h-1. The OR was 6.82 (95% CI: 0.58-79.91) and 12.00 (95% CI: 0.84-172.22) in overall toxicity and BMT, respectively, between patients in TPMT activity<19.18 nmol 6-MTG·gHb-1·h-1 and TPMT activity>19.18 nmol 6-MTG·gHb-1·h-1 group, however, the difference did not reach statistical significance. Only 1 patient (1.3%) had TPMT*3C heterozygous mutation and this patient experienced BMT. Conclusions: This study suggests that TPMT activity and genotype may have correlation with overall thiopurine toxicity and BMT, but its actual clinical value need to be further studied.%背景:嘌呤类药物广泛用于炎症性肠病(IBD)患者的诱导缓解和维持治疗,然而毒副反应的频繁发生使其临床应用受到限制.有研究显示检测硫嘌呤甲基转移酶(TPMT)活性和基因型能预测硫唑嘌呤(AZA)相关的毒副反应.目的:评价TPMT活性和基因型与AZA治疗IBD的毒副反应的关系.方法:收集2008年10月～2010年12月于上海仁济医院确诊并接受AZA治疗(每日1kg)的78例IBD患者.采用高效液相色谱法(HPLC)检测TPMT活性,以直接测序和PCR法检测TPMT基因型.分析TPMT活性和基因型与AZA毒副反应的关系.结果:共19例患者发生毒副反应,包括4例血液学毒副反应.78例IBD患者的平均TPMT活性为(36.10+10.11) nmol 6-MTG·gHb-1·h-1.低TPMT活性组与高TPMT活性组发生总毒副反应和血液学毒副反应的OR值分别为6.82(95％ CI:0.58～79.91)和12.00(95％ CI:0.84～172.22),但差异均无统计学意义.仅1例患者发生TPMT*3C杂合子突变,突变率为1.3％,且该例患者发生了血液学毒副反应.结论:IBD患者的TPMT活性降低和基因突变与嘌呤类药物的总毒副反应和血液学毒副反应可能相关,但其临床实际应用价值有待进一步研究.
展开▼
