Abstract:
Background: 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. Objective: The correlation between N-acetyltransferase 2 (NAT2) genetic polymorphisms and ATDILI was analysed. Methods: 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. Results: The results showed that there were significant differences in the distribution of alleles and acetylation types among different groups (p < 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). Conclusion: 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.
摘要:
背景:考虑到抗结核(TB)药物性肝损伤(ATDILI)患者的遗传特征,遗传因素及其对治疗的影响需要研究。目的:分析N-乙酰转移酶2(NAT2)基因多态性与ATDILI的相关性。方法:在本研究中,对120例TB患者的肝脏和凝血功能进行了至少3个月的动态监测.通过焦磷酸测序检测患者的遗传多态性,并对肝损伤的乙酰化类型和NAT2基因多态性的分布进行比较分析。结果:各组间等位基因分布及乙酰化类型差异有统计学意义(p<0.05)。在4级肝损伤(肝衰竭)的患者中,包括任何两个等位基因,即,*6和*7。具体来说,快速乙酰化基因型患者占42.4%(14/33),中间乙酰化基因型占55.2%(32/58),慢乙酰化基因型患者占65.5%(19/29)。结论:慢乙酰化基因型患者肝衰竭和肝损伤发生率高于中、快乙酰化基因型患者,并且含有任何两个等位基因(*6和*7)的慢乙酰化基因型患者的肝衰竭发生率高于其他等位基因的患者。总之,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肝功能恢复时间短于总平均时间。