N-乙酰基转移酶2基因分型与抗结核药物性肝损伤的关系研究  

Study on correlation of N-acetyltransferase 2 genotyping and anti-tuberculosis drug induced liver injury

作　　者：毛玉巧 邱小惠 何梦玲 付喜花 麦艳君 MAO Yu-qiao;QIU Xiao-hui;HE Meng-ling(Panyu District Central Hospital,Guangzhou 511400,China)

机构地区：[1]广州市番禺区中心医院,511400

出　　处：《中国现代药物应用》2023年第1期20-23,共4页Chinese Journal of Modern Drug Application

基　　金：广州市番禺区科技计划项目(项目编号:2019-Z04-61)。

摘　　要：目的 探讨N-乙酰基转移酶2(NAT2)基因分型与抗结核药物性肝损伤的关系。方法 73例肺结核病初治患者,采用焦磷酸直接测序法进行NAT2基因分型,判定NAT2基因型及代谢表型。分析患者的一般资料、NAT2相关基因多态性分布情况,比较不同NAT2基因代谢分型患者的药物性肝损伤情况及临床效果。结果 本试验纳入初治结核患者73例,其中男54例,女19例,年龄20~89岁,治疗2个月后发生药物性肝损伤22例(30.14%)。药物性肝损伤患者的年龄和基础ALT、AST、谷丙转氨酶(ALT)、谷草转氨酶(AST)、血清总胆红素(TB)水平及随访ALT、AST、碱性磷酸酶(ALP)、TB水平均显著高于无药物性肝损伤患者,差异具有统计学意义(P<0.05);药物性肝损伤患者和无药物性肝损伤患者的性别、基础ALP水平比较差异无统计学意义(P>0.05)。73例患者NAT2基因代谢分型中占比由高到低依次为中间代谢型32例(43.84%)、快代谢型24例(32.88%)、慢代谢型17例(23.29%);药物性肝损伤患者和无药物性肝损伤患者的NAT2基因代谢分型比较差异具有统计学意义(P<0.05)。快代谢型患者发生药物性肝损伤的风险最低(OR=0.344, P=0.079>0.05),而慢代谢型患者出现药物性肝损伤的风险最高(OR=5.238, P=0.003<0.05)。所有患者随访2个月,总好转率为65.75%(48/73),其中慢代谢型患者的治疗好转率88.24%(15/17)明显高于快代谢型的58.33%(14/24)、中间代谢型的59.38%(19/32),差异有统计学意义(P<0.05)。结论 为降低结核患者药物性肝损伤发生率及提高结核病治疗效果,临床医生可根据NAT2基因不同分型合理调整异烟肼(INH)药物使用剂量。Objective To discuss the correlation of N-acetyltransferase 2(NAT2) genotyping and antituberculosis drug induced liver injury. Methods 73 patients with primary treatment of pulmonary tuberculosis received NAT2 genotyping by direct pyrophosphate sequencing to determine the NAT2 genotype and metabolic phenotype. The general data of patients and the distribution of NAT2 related gene polymorphisms were analyzed,and the drug-induced liver injury and clinical effects of patients with different metabolic phenotypes of NAT2gene were compared. Results 73 patients with primary treatment of pulmonary tuberculosis were included in this trial, including 54 males and 19 females, aged 20-89 years, with 22 cases(30.14%) of drug-induced liver injury occurring after 2 months of treatment. The age and basal ALT, AST, and TB levels and follow-up ALT,AST, ALP, and TB levels of patients with drug-induced liver injury were significantly higher than those of patients without drug-induced liver injury, and the differences were statistically significant(P<0.05). The differences in gender and basal ALP levels between patients with and without drug-induced liver injury were not statistically significant(P>0.05). The proportion of metabolic phenotypes of NAT2 gene in 73 patients from high to low was intermediate metabolizer in 32 cases(43.84%), extensive metabolizer in 24 cases(32.88%), poor metabolizer in 17 cases(23.29%). The differences in metabolic phenotypes of NAT2 gene between patients with and without drug-related liver injury were statistically significant(P<0.05). Patients with extensive metabolizer had the lowest risk of drug-induced liver injury(OR=0.344, P=0.079>0.05), while patients with poor metabolizer had the highest risk of drug-induced liver injury(OR=5.238, P=0.003<0.05). The overall improvement rate of all patients at 2-month follow-up was 65.75%(48/73). The treatment improvement rate was 88.24%(15/17) in patients with poor metabolizer, which was significantly higher than 58.33%(14/24) in patients with extensive metaboli

关 键 词：N-乙酰基转移酶2 异烟肼 基因多态性 药物性肝损伤 

分 类 号：R521[医药卫生—内科学] R575[医药卫生—临床医学]