rs1495741单核苷酸多态性与抗结核药物性肝损害的相关性研究

Association of rs1495741 Single Nucleotide Polymorphism with Susceptibility of Anti-tuberculosis Drug-induced Hepatotoxicity

中文关键词:  N-乙酰基转移酶2 抗结核药物性肝损害 肺结核

英文关键词:N-acetyltransferase 2 Anti-tuberculosis drug-induced hepatotoxicity Pulmonary tuberculosis

中文摘要:

      目的 探讨N-乙酰基转移酶2（NAT2）基因多态性与抗结核药物性肝损害（ATDH）易感性的关系。方法 采用改良多重连接酶检测反应检测结核病患者NAT2 rs1495741位点的基因多态性。采用logistic回归分析多态性位点与ATDH的易感性。结果 对符合纳入标准的247例结核患者进行分析，发生ATDH 24例，未发生ATDH 223例。NAT2 rs1495741位点等位基因和基因型频率在两组间分布差异无统计学意义。 校正年龄、性别、体质量指数（BMI）及吸烟史后，隐性模型（AA vs. GA+GG）分析结果显示rs1495741与ATDH的发生风险增高相关〔比值比（OR）=2.728，95%可信区间：1.022～7.281〕。结论 汉族人群NAT2基因多态性与ATDH的发生密切相关，携带AA基因型的结核病患者更易发生ATDH。

英文摘要:

      Objective To investigate the potential association between the polymorphism of N- acetyltransferase 2 (NAT2) gene and anti-tuberculosis drug-induced hepatotoxicity (ATDH) in Han population. Methods The SNP rs1495741 was genotyped by using multiplex ligation detection reaction (MLDR) technique, and logistic regression analysis was used to analyze the association between this SNP and the susceptibility of ATDH. Results There were 247 PTB patients enrolled in this study, including 24 ATDH, and 223 controls (PTB without ATDH). No significant difference in genotype and allele distribution was observed for rs1495741 in NAT2 between the controls and ATDH group. After adjusting age, sex, body mass index (BMI) and smoking history, the SNP of rs1495741 showed a significant association with ATDH 〔odds ratio (OR)=2.728 (95% confidence interval: 1.022-7.281)〕 under recessive model （AA vs. GA+GG）. Conclusion The rs1495741 in NAT2 seems related to the development of ATDH among PTB patients, AA genotype of rs1495741 may be a causative factor for increased susceptibility to ATDH.