Cheng Fang, Jiang Xian-Gao, Zheng Shi-Lin, Wu Te, Zhang Qiang, Ye Xin-Chun, Liu Saiduo, Shi Ji-Chan
Department of Infectious Disease of Wenzhou Central Hospital, Wenzhou Central Hospital, The Dingli Clinical College of Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2023 Aug 31;14:1171353. doi: 10.3389/fphar.2023.1171353. eCollection 2023.
Considering the genetic characteristics of people with anti-tuberculosis (TB)-drug-induced liver injury (ATDILI), genetic factors and their consequences for treatment need to be studied. The correlation between N-acetyltransferase 2 (NAT2) genetic polymorphisms and ATDILI was analysed. In this study, the liver and coagulation functions of 120 patients with TB were monitored dynamically for at least 3 months. The genetic polymorphisms of patients were detected by pyrosequencing, and the acetylation types of liver damage and the distribution of NAT2 genetic polymorphisms were compared and analysed. The results showed that there were significant differences in the distribution of alleles and acetylation types among different groups ( < 0.05). In patients with grade 4 liver injury (liver failure), any two alleles were included, i.e., *6 and *7. Specifically, patients with fast acetylation genotypes accounted for 42.4% (14/33), those with intermediate acetylated genotypes accounted for 55.2% (32/58), and patients with slow acetylation genotypes accounted for 65.5% (19/29). Patients with slow acetylation genotypes had higher rates of liver failure and liver injury than those with intermediate and fast acetylation genotypes, and patients with slow acetylation genotypes containing any two alleles (*6 and *7) had a higher rate of liver failure than those with other alleles. In summary, the time of liver injury in patients with slow acetylation genotypes was earlier than the total average time, and the time of liver function recovery in patients with fast acetylation genotypes was shorter than the total average time.
考虑到抗结核药物性肝损伤（ATDILI）患者的遗传特征，需要研究遗传因素及其对治疗的影响。分析了N - 乙酰基转移酶2（NAT2）基因多态性与ATDILI之间的相关性。本研究对120例结核病患者的肝脏和凝血功能进行了至少3个月的动态监测。采用焦磷酸测序法检测患者的基因多态性，并比较分析肝损伤的乙酰化类型和NAT2基因多态性的分布情况。结果显示，不同组间等位基因分布和乙酰化类型存在显著差异（<0.05）。在4级肝损伤（肝衰竭）患者中，包含任意两个等位基因，即6和7。具体而言，快速乙酰化基因型患者占42.4%（14/33），中等乙酰化基因型患者占55.2%（32/58），缓慢乙酰化基因型患者占65.5%（19/29）。缓慢乙酰化基因型患者的肝衰竭和肝损伤发生率高于中等和快速乙酰化基因型患者，且包含任意两个等位基因（6和7）的缓慢乙酰化基因型患者的肝衰竭发生率高于其他等位基因患者。综上所述，缓慢乙酰化基因型患者的肝损伤时间早于总平均时间，快速乙酰化基因型患者的肝功能恢复时间短于总平均时间。
