TPMT基因多态性与炎症性肠病治疗中硫唑嘌呤毒副反应相关性的荟萃分析

硫唑嘌呤(AZA)广泛用于炎症性肠病(IBD)的诱导缓解和维持治疗,然而AZA的毒副反应在很大程度上限制了其应用。目前对硫嘌呤甲基转移酶(TPMT)基因多态性判断AZA毒副反应的研究仍存在争议。目的:系统性评价IBD患者TPMT基因多态性与AZA治疗毒副反应的相关性。方法:从电子数据库中检索有关TPMT基因多态性与AZA耐受和不耐受的成人IBD患者之间关系的研究,荟萃分析各项研究中发生与未发生AZA总毒副反应、血液学毒副反应、肝脏毒副反应和胰腺炎的IBD患者TPMT基因突变率的OR值;并行敏感性分析;以漏斗图检测发表偏倚。结果:共8项(1322例IBD患者)回顾性研究符合纳入标准。发生总毒副反应和血液学毒副反应的IBD患者与未发生相应毒副反应者的TPMT基因突变率的OR值分别2.93(95%CI:1.68～5.09,P0.01)和5.82(95%CI:2.9311.55,P0.01)。发生肝脏毒副反应和胰腺炎的IBD患者与未发生相应毒副反应者的TPMT基因突变率的OR值分别为1.51(95%CI:0.54～4.19,P=0.43)和1.02(95%CI:0.26～3.99,P=0.98)。结论:IBD患者的TPMT基因多态性与AZA的总毒副反应和血液学毒副反应相关,但与肝脏毒副反应和胰腺炎无关。

Correlation between TPMT Polymorphisms and Azathioprine Toxicity in the Treatment of Inflammatory Bowel Disease: A Meta Analysis

Background： The efficacy of azathioprine （AZA） in the treatment of inflammatory bowel disease （IBD） is well established. However, severe side effects limit its use in some patients. The impact of thiopurine S-methyhransferase （TPMT） polymorphisms on AZA toxicity has been evaluated in several studies but with varying outcomes. Aims： To systematically evaluate the correlation between TPMT polymorphisms and AZA-induced side effects in IBD patients. Methods： Eligible articles that compared TPMT polymorphisms between AZA-tolerant and -intolerant adult IBD patients were collected from electronic databases. The outcome measure examined was the OR for TPMT gene mutation rate between IBD patients with and without AZA-induced overall side effects, bone marrow toxicity, hepatotoxicity and pancreatitis. Sensitivity analysis was also performed. The publication bias was tested by funnel plot. Results： Eight studies including a total of 1322 participants met our inclusion criteria. The OR for TPMT gene mutation rate between IBD patients with and without AZA-induced overall side effects and bone marrow toxicity were 2.93 （95% CI： 1.68-5.09, P〈0.01） and 5.82 （95% CI： 2.93-11.55, P〈0.01）, respectively. The OR for TPMT gene mutation rate between IBD patients with and without AZA-induced hepatotoxicity and pancreatitis were 1.51 （95% CI： 0.54-4.19, P=0.43） and 1.02 （95% CI： 0.26-3.99, P=0.98）, respectively. Conclusions： TPMT polymorphisms are associated with AZA-induced overall side effects and bone marrow toxicity, but not with hepatotoxicity and pancreatitis.