有机阴离子转运多肽1B1基因多态性和利福平血药浓度对肝毒性的影响  

Effects of organic anion transporting polypeptide 1B1 polymorphism and plasma concentration of rifampicin on liver in- jury

作　　者：邓国防[1] 孙丽珍[1] 詹森林[1] 李巍[2] 吴于青[3] 邓群[3] 雷建平[3] 余少良 

机构地区：[1]广东医学院附属深圳市第三人民医院肺二科,518112 [2]广东医学院附属深圳市第三人民医院药剂科,518112 [3]江西省胸科医院结核科 [4]江西省胸科医院心内科

出　　处：《中国防痨杂志》2015年第9期933-937,共5页Chinese Journal of Antituberculosis

基　　金：江西省自然科学基金（20132BAB205013）

摘　　要：目的观察有机阴离子转运多肽181（OTP1B1，又称编码基因SLCO181）A388G基因多态性和利福平血药浓度对肝脏毒性的影响。方法选择2013年9月至2014年3月来自深圳市第三人民医院住院或门诊接受治疗的汉族患者，服用含利福平药物肝功能异常的肺结核患者（简称“异常组”）和服用含利福平药物肝功能正常的肺结核患者（简称“正常组”）各30例，其中正常组：男19例，女11例，平均年龄（37．70±11．78）岁；异常组：男21例，女9例，平均年龄（38．60±11．56）岁。分别进行OATP1B1A388G基因分型和利福平血药浓度检测，使用GraphPadPrism5进行统计学处理，采用y。检验比较正常组与异常组的等位基因频率差异，以t检验比较正常组与异常组利福平血药浓度差异，P〈0．05作为差异有统计学意义。结果正常组患者OATP1B1A388G基因rs2306283位点基因频率分布A：36．7％（22／60），G：63．3％（38／60），异常组A：23．3％（14／60），G：76．7％（46／60），差异无统计学意义（X2=4，P〉0．05）；正常组患者利福平血药浓度检测结果为（69．36±28．85）mg／L，异常组为（33．20±19．88）mg／L，差异有统计学意义（t=3．16，P〈0．05）。结论OATPIBlA388G基因多态性分布与服用含利福平药物的肝毒性无明显相关，而利福平血药浓度与肝毒性呈明显相关，应加强对利福平血药浓度监测，降低患者肝毒性。Objective To observe the effects of organic anion transporting polypeptide 1B1 （OATP1B1, en- coded by SLCO1B1） A388G polymorphism and the plasma concentration of rifampicin on drug （rifampicin）-induced liver injury. Methods Thirty pulmonary tuberculosis patients with drug （rifampicin）-induced liver injury （abnor- mal group）, and 30 pulmonary tuberculosis patients without drug （rifampicin）-induced liver injury （normal group） treated with antituberculous regimen containing rifampicin were recruited from the third people＇s Hospital of Shenzhen inpatients or outpatients of Han nationality from September 2013 to March 2014. In the normal group, there were 19 males and 11 females, with average age （37.70±11.78） years. In the abnormal group, 21 males and 9 females, with average age （38.60± 11.56） years. TaqMan probe was designed and real-time PCR was used to detect OATP1B1 A388G genotype polymorphism. The plasma concentration of rifampicin was detected by high perfor- mance liquid chromatography （HPLC）. Using GraphPad Prism 5 software for statistical analysis. Using X2 test com- pared allelic gene frequency difference and using t-test compared rifampicin blood drug concentration difference between the normal group and abnormal group. P〈0. 05 was considered statistically significant. Results OATP1B1 A388G genotypes existed allele frequency A.. 36.7% （22/60）, G： 63.3G （38/60） in normal group and A.- 23.3% （14/60） ,G： 76.7G （46/60） in abnormal group. The difference was not statistically significant between abnormal group and normal group（X2=-2.54,P〉0.05）. The plasma concentration of rifampicin was （69.36±28.85） mg/L in normal group, （33.20± 19.88） mg/L in abnormal group, the difference was statistically significant （t= 13.16, P〈0. 05）. Conclusion OATPIB1 A388G gene polymorphism is not associated with drug （rifampicin）-induced liver iniury, and the plasma concentration of rifampiein is significantly associated with drug （rifampicin）-

关 键 词：有机阴离子转运子 多态性 单核苷酸 利福平 血药浓度 药物性肝损伤 

分 类 号：R333.4[医药卫生—人体生理学]