NAT2基因多态性与异烟肼药物性肝损伤的相关性分析

Polymorphisms of NAT2 related to Isoniazid-induced liver injury in tuberculosis patients

目的分析抗结核治疗肝损害患者NAT2的基因多态性,探讨NAT2基因多态性与异烟肼药物性肝损害之间的分子机制,为肝损害的防治提供参考。方法选取潍坊市第二人民医院2019年11月至2020年12月期间诊断为肺结核并行规范化治疗的235例病例,将抗结核药物治疗6个月内发生肝损伤的结核病初治的115例患者作为病例组,抗结核治疗6个月内未发生肝损伤的结核病初治的120例患者作为对照组。采用MGB探针设计检测患者NAT2的基因多态性。观察异烟肼药物致肝损伤与NAT2基因的不同单核苷酸多态性之间的关系,比较病例组和对照组中NAT2基因多态性的分布规律。结果病例组与对照组在年龄、性别、吸烟、饮酒上比较,差异无统计学意义(P>0.05)。病例组在rs1041983(282C>T)、rs1801280(341T>C)、rs1799930(590G>A)、rs1799931(857G>A)的基因突变型比例明显高于对照组,差异有统计学意义(P<0.05)。NAT2基因突变型检测诊断结核药物致肝损伤时灵敏度为76.5%(88/115),特异性为77.5%(93/120),阳性预测值为76.5%(88/115),阴性预测值为77.5%(93/120)。结论NAT2基因多态性可以作为异烟肼药物引发的肝损伤的分子标记。

Objective To analyze the molecular mechanism of NAT2 in patients with Isoniazid-induced liver injury treated with antituberculosis therapy and to explore the relationship between polymorphisms of NAT2 and liver injury.Methods A total of 235 cases diagnosed with pulmonary tuberculosis and receiving standardized treatment from November 2019 to December 2020 in the Second People’s Hospital of Weifang City were selected,a total of 115 newly-treated tuberculosis patients with liver injury within 6 months of antituberculosis drug treatment were selected as the case group,and 120 newly-treated tuberculosis patients without liver injury within 6 months of anti-tuberculosis treatment were selected as the control group.The MGB probe was designed to detect polymorphism in patients with NAT2.To observe the relationship between isoniazid-induced liver injury and different single nucleotide polymorphisms of NAT2 gene,and to compare the distribution of NAT2 gene polymorphisms in case group and control group.Results There was no significant difference between the case group and the control group in age,gender,smoking and drinking(P>0.05).The mutation rates of rs1041983(282 C>T),rs1801280(341 T>C),rs1799930(590 G>A),rs1799931(857 G>A)in the case group were significantly higher than those in the Control Group(P<0.05).The sensitivity of NAT2 gene mutation detection in the diagnosis of liver injury caused by tuberculosis drugs was 76.5%(88/115),the specificity was 77.5%(93/120),the positive predictive value was 76.5%(88/115),and the negative predictive value was 77.5%(93/120).Conclusion Polymorphisms of NAT2 can be used as a molecular marker of Isoniazid-induced liver injury in tuberculosis patients.