中国临床药理学杂志2018，Vol.34Issue(6)：660-662,3.DOI:10.13699/j.cnki.1001-6821.2018.06.015
OATP1B1基因多态性与利福平临床肝毒性的相关性研究
Correlation study about the genetic ploymorphisms of OATP1B1 and clinical hepatotoxicity induced by rifampicin
摘要
Abstract
Objective To explore the correlation between the genetic polymorphisms of organic anion-transporting polypeptide (OATP1B1),steady-state trough concentrations of rifampicin and the occurrence of hepatotoxicity induced by rifampicin.Methods Ninety tuberculosis (TB) patients were continuously administrated equal doses of rifampicin,34 cases developed drug-induced liver injury (DILI),while 56 had non drug-induced liver injury (non-DILI).Then trough concentrations of rifampicin in these subjects were determined by LC-MS/MS,and OATP1B1 388A ＞ G genotyping was obtained by polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) methods.Finally,the correlations analysis were undertaken between the genetic polymorphisms of OATP1B1,steady-state trough concentrations of rifampicin and incidence of hepatotoxicity induced by rifampicin.Results There were 68 patients carrying wild-type genotypes and 22 carrying mutant genotypes in 90 subjects,with mutation rate of 24.44％.In which,mutant genotypes rates were 8.82％ (3 cases/34 cases) and 33.93％ (19 cases/56 cases) in DILI group and non-DILI group.Rifampicin trough concentration of patients with mutant genotypes was (5.63 ±4.16) ng· mL-1,3.43 times that of wild-type genotypes,which was (1.64 ±4.81) ng · mL-1.Likewise,concentration of rifampicin in non-DILI group was (3.82 ± 5.80) ng · mL-1,5.97 times that of DILI group,which was (0.64 ± 1.85) ng · mL-1.Mutation rate of OATP1B1 388A ＞ G in non-DILI group was 33.93％,3.85 times that in DILI group.The incidence of hepatotoxicity in patients carrying wild-type genotype was 45.59％,amounting to 3.34 times that of mutant genotypes.Conclusion Genetic polymorphisms of OATP1B1 may have significant impacts on steady-state trough concentration of rifampicin in Chinese patients and the occurrence of hepatotoxicity.关键词
利福平/肝毒性/基因多态性Key words
rifampicin/hepatotoxicity/genetic polymorphisms分类
医药卫生引用本文复制引用
刘瑜,陈琳,杨发有,袁小兰,邓国防,夏春华..OATP1B1基因多态性与利福平临床肝毒性的相关性研究[J].中国临床药理学杂志,2018,34(6):660-662,3.基金项目
国家自然科学基金资助项目(81060275,81160411) （81060275,81160411）
江西省自然科学基金资助项目(20132BAB205013) （20132BAB205013）
江西省科技支撑计划基金资助项目(20132BBG70100) （20132BBG70100）
江西省青年科学家培养对象基金资助项目(20133BCB23006) （20133BCB23006）
