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目的 考察有机阴离子转运多肽1B1(OATP1B1)基因多态性、利福平稳态谷浓度及肝毒性之间的相关性.方法 入选90例结核病患者,连续多次服用同等剂量的利福平,34例患者出现肝损伤,56例患者未出现肝损伤,用液质联用法测定利福平稳态谷浓度,用限制性片段长度多态性聚合酶链反应方法(RFLP PCR)对OATP1B1 388A＞G进行基因分型,对OATP1B1 388A＞G不同基因型与利福平血药浓度、肝毒性的相关性进行分析.结果 90例患者中,OATP1B1388A＞G总野生型68例,总突变型22例,总突变率为24.44％,其中肝损伤组突变型3例,肝功能正常组突变型19例.突变型个体利福平谷浓度为(5.63±4.16)ng·mL-1,野生型个体利福平谷浓度为(1.64 ±4.81)ng·mL-1,前者约为后者的3.43倍;肝功能正常组利福平谷浓度为(3.82±5.80)ng·mL-1,肝损伤组利福平谷浓度为(0.64±1.85)ng·mL-1,前者相当于后者的5.97倍;肝功能正常组OATP1B1 388A＞G突变率为33.93％,为肝损伤组的3.85倍;野生型患者肝损伤发生率为45.59％,相当于突变型患者的3.34倍.结论 OATP1B1 388A＞G基因位点突变对中国人体内利福平的稳态谷浓度、肝毒性的发生有显著影响.“,”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.