亚洲炎症性肠病患者TPMT基因突变增加嘌呤类药物不良反应的Meta分析  

Thiopurine S-methyltransferase polymorphisms increase thiopurine toxicity in Asian patients with inflammatory bowel disease: A meta-analysis

作　　者：董显文[1] 黄莎[1] 黄诗良[1] 张学松[1] DONG Xianwen;HUANG Sha;HUANG Shiliang(Department of Gastroenterology, Lihuili Hospital of Ningbo Medical Center, Ningbo 315040, China)

机构地区：[1]宁波市医疗中心李惠利医院消化科,315040

出　　处：《浙江医学》2019年第10期1049-1052,1061,共5页Zhejiang Medical Journal

基　　金：宁波市科技项目(2015A610175)

摘　　要：目的探讨亚洲黄种人炎症性肠病(IBD)患者硫嘌呤甲基转移酶(TPMT)基因多态性与嘌呤类药物不良反应(ADR)之间的关系。方法分别以"thiopurine S-methyltransferase"、"inflammatory bowel disease/ulcerative colitis/crohn’s disease"和"thiopurine/azathioprine/6-mercaptopurine"及"TPMT"、"IBD/溃疡性结肠炎/克罗恩病"和"硫唑嘌呤/6-甲巯基嘌呤"为检索词,在PubMed、EMBASE、Cochrane Central Register of Controlled Trials、Science Citation Index、Wiley InterScience和Ovid及万方数据库、维普数据库和中国知网中检索有关研究,Meta分析嘌呤类药物耐受与不耐受的亚洲黄种人IBD患者TMPT基因突变率的优势比(OR);采用RevMan5.0软件进行分析,并绘制漏斗图检测有无发表偏倚。结果 9项研究共计2 127例IBD患者纳入。总ADR组和血液学不良反应组患者TPMT基因突变率明显高于对照组,OR值分别为10.12(95%CI:2.01～50.94, P<0.01)和6.21(95%CI:1.93～20.01, P<0.01)。共有7例IBD患者发生嘌呤类药物相关肝脏不良反应,这些患者均为TPMT野生型纯合子个体。结论亚洲黄种人IBD患者TPMT基因突变将导致嘌呤类药物ADR,尤其是血液学不良反应显著增加,其临床实际运用价值尚有待研究进一步评价。Objective To investigate the association of thiopurine S-methyltransferase(TPMT) polymorphisms and thiopurine toxicity in Asian patients with inflammatory bowel diseases(IBD). Methods Electronic databases for articles that compared the frequencies of TPMT polymorphisms among thiopurines-tolerant and -intolerant adult Asian IBD patients were searched. The key words of thiopurine S-methyltransferase, inflammatory bowel disease/ulcerative colitis/Crohn's disease and thiopurine/azathioprine/6-mercaptopurine were used for search. The publication bias was assessed through visual inspection of funnel plot. The odds ratio (OR) of TMPT mutation in intolerant patients was compared with tolerant patients. A meta-analysis was performed by Revman 5.0. Results Nine studies with a total of 2 127 patients with IBD were identified. The thiopurines-induced total adverse disease rate (ADR)(OR=10.12, 95%CI:2.01~50.94, P<0.01) and bone marrow toxicity(OR=6.21, 95%CI:1.93~20.01, P<0.01) in TPMT mutation patients were significantly higher than those in non-TPMT mutation patients. The thiopurines-induced hepatotoxicity developed in 7 IBD patients, who were all of TPMT wild-type. Conclusion TPMT polymorphisms are associated with thiopurines-induced total ADR and bone marrow toxicity in Asian IBD patients, the clinical application of TPMT genotype screening before thiopurines drug therapy need to be further studied.

关 键 词：硫嘌呤甲基转移酶 基因多态性 炎症性肠病 不良反应 嘌呤类药物 

分 类 号：R574[医药卫生—消化系统]