NAT2基因多态性在藏汉结核患者间的分布及抗结核药物诱导肝损伤的相关性研究  

Distribution of NAT2 gene ploymorphism among Tibetan and Han Tuberculosis patients and its correlation with anti-TB drug-induced liver injury

作　　者：徐娜 何霞[3,4] 李星星 张雪 张敏[1,2,4] XU Na;HE Xia;LI Xing-xing;ZHANG Xue;ZHANG Min(School of Pharmacy,Chendu University of Traditional Chinese Medicine,Chendu 611137,Sichuan Province,China;Department of Pharmacy,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610071,Sichuan Province,China;Department of Pharmacy,Sichuan Provincial Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Chengdu 610072,Sichuan Province,China;Dersonalized Drug Therapy Key Laboratory of Sichuan Province,School of Medicine,University of Electronic Science and Technology of China,Chengdu 610072,Sichuan Province,China)

机构地区：[1]成都中医药大学药学院,四川成都611137 [2]成都中医药大学附属医院药剂科,四川成都610071 [3]四川省医学科学院·四川省人民医院药学部,四川成都610072 [4]电子科技大学医学院个体化药物治疗四川省重点实验室,四川成都610072

出　　处：《中国临床药理学杂志》2022年第21期2531-2535,共5页The Chinese Journal of Clinical Pharmacology

基　　金：四川省科技计划基金资助项目(2019YJ0575);四川省卫生与健康委员会普及应用基金资助项目(18PJ544)。

摘　　要：目的研究N-乙酰基转移酶2(NAT2)基因多态性在藏汉结核患者间的分布,以及与抗结核药物诱导肝损伤(AT-DILI)的相关性。方法纳入诊断为结核的住院治疗患者146例为研究对象。以荧光定量聚合酶链反应(PCR)探针法测定NAT2基因多态性。依据是否发生肝损伤,分为试验组(肝损伤组)和对照组(未发生肝损伤组),收集2组患者基本资料进行统计学分析NAT2基因多态性在藏汉结核患者间的分布及AT-DILI的相关性。结果纳入对象146例(汉族78例,藏族68例),试验组31例,对照组115例。NAT2中乙酰化型(IA)42例(28.8%)、慢乙酰化型(SA)28例(19.2%)和快乙酰化型(RA)76例(52.0%),5个等位基因NAT2*4、NAT2*6A、NAT2*7B、NAT2*5B、NAT2*6B基因分布分别为54.8%,24.7%,16.4%,3.8%,0.3%。NAT2基因多态性在藏族和汉族患者间分布差异有统计学意义(P<0.05),藏汉两组IA型患者在试验组和对照组间比较差异有统计学意义(P<0.05),SA型的*6A等位基因在试验组和对照组间差异有统计学意义(P<0.05)。结论NAT2基因多态性在藏汉族结核患者中的分布存在差异是藏汉民族间AT-DILI差异的重要影响因素之一。Objective To study the distribution of N-acetylgenase 2(NAT2)gene polymorphism among Tibetan and Han patients with tuberculosis,and the correlation with anti-TB drug-induced liver injury(AT-DILI).Methods A total of 146 cases of patients who diagnosed with tuberculosisin were included.NAT2 gene polymorphism was determined by fluorescence quantitative polymerase chain reaction probe.Based on whether liver injury occurred,it was divided into treatment group(liver injury group)and control group(no liver injury group),and the basic information about both groups of patients were collected for statistical analysis of the distribution of NAT2 gene polymorphism among Tibetan and Han patients with TB and the correlation between AT-DILI.Results A total of 146 cases(Han 78 cases,Tibetan 68 cases),31 patients were in treatment group and 115 patients were in control group.In NAT2,there were 42 cases(28.8%)of intermediate acetylator(IA),28 cases(19.2%)of slow acetylator(SA)and 76 cases(52.0%)of rapid acetylator type(RA).The distribution of 5 allelesNAT2*4,NAT2*6A,NAT2*7B,NAT2*5B and NAT2*6Bwere 54.8%,24.7%,16.4%,3.8%and 0.3%,respectively.The differences in the distribution ofNAT2 gene polymorphism among Tibetan and Han patients were statistically significant(P<0.05),there were statistically significant difference between treatment group and control group in patients with type IA between Tibetan and Han groups(P<0.05),and the differences of the*6A allele of SA type between the treatment group and the control group were statistically significant(P<0.05).Conclusion The difference in distribution ofNAT2 gene polymorphism in Tibetan and Han tuberculosis patients is one of the important influencing factors of the difference of AT-DIDI between Tibetan and Han nationalities.

关 键 词：结核病 N-乙酰基转移酶2 基因多态性 抗结核药物诱导肝损伤 

分 类 号：R978.3[医药卫生—药品]