N－乙酰基转移酶2基因多态性与抗结核药所致肝损害的关系  

Association between polymorphism of N-acetyltransferase 2 gene and development of antituberculosis drug-induced liver injury

作　　者：黄冬生[1] 邹永红[2] 何刚[3] 吕嘉春[4] 王云南[1] 

机构地区：[1]广州市胸科医院呼吸内科,510095 [2]广州市胸科医院结核内科,510095 [3]广州市胸科医院第二门诊部,510095 [4]广州医学院公共卫生学院

出　　处：《中华生物医学工程杂志》2011年第5期444-447,共4页Chinese Journal of Biomedical Engineering

基　　金：广东省科技计划项目（20088030301265）

摘　　要：目的 研究N-乙酰基转移酶2（NAT2）的多态性与抗结核药物所致肝损害发病的关联.方法 应用病例对照研究方法.采用PCR-测序技术检测119例抗结核药物性肝损害和198例抗结核药物治疗无肝损害的对照组NAT2基因的基因型.用SAS9.13软件分析该基因变异与抗结核药物性肝损害发病的关联.结果 根据基因表型的代谢速度将NAT2分为快型（4/4）、中间型（4/5A、4/5B、4/5C、4/6、4/7）、慢型（5B/6、5B/7、6/6、6/7、7/7）3类.肝损害组和对照组间基因表型频率差异有统计学意义（P＜0.05）.logistics回归分析表明,慢型患者出现肝损害的危险性是快型＋中间型的1.91倍（95％CI,1.10～3.33）.分层分析发现,年龄≤40岁和痰涂片阴性的慢型基因型患者更容易出现肝损害（P＜0.05）.结论 抗结核药物所致肝损害发生与可能NAT2基因的多态性有关,慢型患者较快型＋中间型患者更易出现肝损害.Objective To study the association between the polymorphism of N-acetyltransterase 2（NAT2） gene and antituberculosis drug-induced liver injury （ATLI）.Methods In this case-control study,the NAT2 genotypes of 119 pulmonary tuberculosis patients with ATLI and 198 patients without ATLI were analyzed by PCR sequencing technique.The association between NAT2 polymorphism and ATLI was examined by SAS9.13 software.Results The NAT2 was divided into three types according to metabolism rate of their gene phenotype： rapid type （4/4）,intermediate type （4/5A,4/5B,4/5C,4/6,4/7） and slow type （5B/6,5B/7,6/6,6/7,7/7）.There was a significant statistical difference in genotype frequency between the two groups of patients （P〈0.05）.Logistics regression analysis demonstrated that the ATLI risk individuals with slow-type NAT2 was 1.91 times of intermediate- and rapid-type patients combined （OR,1.91 ; 95% CI,1.10-3.33）.Further,stratification analysis showed that slow-type subjects aged older than 40with negative sputum smear were more likely to have liver injury （P〈0.05）.Conclusion ATLI is associated with NAT2 genotype,and therefore NAT2 genotyping before antituberculotic medication is recommended for guiding clinical practices.

关 键 词：抗结核药 乙酰基转移酶类 单核苷酸多态性 药物性肝损伤 肺结核 

分 类 号：R595.3[医药卫生—内科学]