NAT2基因多态性与异烟肼血药浓度关系的研究

Study on the Relationship between NAT2 Gene Polymorphism and Isoniazid DrugConcentration in Blood

摘要: 目的：通过对肺结核患者进行异烟肼血药浓度监测，以及NAT2基因多态性检测，探讨NAT2基因多态性与异烟肼血药浓度之间的关系。方法：研究对象为昆明市第三人民医院2020年结核科诊断为初治肺结核的患者，共纳入62例，规律口服异烟肼5天，用药后2 h采外周静脉血检测其血药浓度，同时提取DNA，用Sanger法进行NAT2基因多态性分析；SPSS 22 Pearson相关性分析影响异烟肼血药浓度的因素(包括性别、年龄、体重、NAT2基因多态性)。结果：性别、年龄、体重与异烟肼血药浓度不具有相关性，而NAT2代谢型异烟肼血药浓度具有相关性；62例患者中，NAT2快代谢型22例(35.5%)，中间代谢型29例(46.8%)，慢代谢型11例(17.7%)；11例慢代谢型患者中，NAT2*6A*6A有6例，占比54.5%，NAT2*7B*7B有4例，占比36.4%，NAT2*5B*5B有1例，占比9.1%。Pearson相关性分析提示，NAT2基因多态性与异烟肼血药浓度具有相关性，P = 0.03。结论：NAT2*6A*6A与NAT2*7B*7B基因型可能为主要的NAT2慢代谢型，携带该等位基因的患者易导致异烟肼血药浓度偏高；NAT2基因多态性与异烟肼血药浓度具有相关性。NAT2基因多态性是影响异烟肼血药浓度的重要因素之一，临床在使用异烟肼时可根据NAT2基因多态性调整用药剂量，同时监测其血药浓度以达到更精准的治疗方案。

Abstract: Objective: The relationship between NAT2 gene polymorphism and isoniazid drug concentration in blood was investigated by monitoring isoniazid drug concentration in blood and detecting NAT2 gene polymorphism in patients with pulmonary tuberculosis. Methods: A total of 62 patients diagnosed with newly treated tuberculosis in the tuberculosis Department of Kunming Third People’s Hospital in 2020 were included in the study. Isoniazid was taken orally for 5 days, and peripheral venous blood was collected 2 hours after administration to detect the drug concentration in blood. Meanwhile, DNA was extracted and NAT2 gene polymorphism was analyzed by the Sanger method. SPSS 22 Pearson correlation analysis was performed to analyze the factors influencing isoniazid drug concentration in blood (including sex, age, weight, NAT2 gene polymorphism). Results: There was no correlation between sex, age and body weight and isoniazid drug concentration in blood, but there was a correlation between NAT2 metabolism isoniazid drug concentration in blood. Among the 62 patients, there were 22 NAT2 fast metabolizers (35.5%), 29 NAT2 intermediate metabolizers (46.8%) and 11 NAT2 slow metabolizers (17.7%). Among the 11 patients with slow metabolism, there were 6 cases of NAT2*6A*6A, accounting for 54.5%, 4 cases of NAT2*7B*7B, accounting for 36.4%, and 1 case of NAT2*5B*5B, accounting for 9.1%. Pearson correlation analysis showed that the polymorphism of NAT2 gene was correlated with isoniazid drug concentration in blood (P = 0.03). Conclusions: The NAT2*6A*6A and NAT2*7B*7B genotypes may be the main slow metabolizers of NAT2, and patients carrying this allele are prone to high drug concentration in blood of isoniazid. There was a correlation between NAT2 gene polymorphism and isoniazid drug concentration in blood. NAT2 gene polymorphism is one of the important factors affecting the drug concentration in blood of isoniazid. In clinical use of isoniazid, the dose can be adjusted according to the NAT2 gene polymorphism, and the drug concentration in blood can be monitored to achieve a more accurate treatment plan.