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王萍玉, 谢书阳, 张功文, 郝青. NAT2基因多态性与肝毒性巢式病例对照研究[J]. 中国公共卫生, 2009, 25(3): 300-302. DOI: 10.11847/zgggws2009-25-03-25
引用本文: 王萍玉, 谢书阳, 张功文, 郝青. NAT2基因多态性与肝毒性巢式病例对照研究[J]. 中国公共卫生, 2009, 25(3): 300-302. DOI: 10.11847/zgggws2009-25-03-25
WANG Ping-yu, XIE Shu-yang, ZHANG Gong-wen, . Prospective nested case-control study on relation between N-acetyltransferase-2 acetylator phenotype and hepatotoxicity in China[J]. Chinese Journal of Public Health, 2009, 25(3): 300-302. DOI: 10.11847/zgggws2009-25-03-25
Citation: WANG Ping-yu, XIE Shu-yang, ZHANG Gong-wen, . Prospective nested case-control study on relation between N-acetyltransferase-2 acetylator phenotype and hepatotoxicity in China[J]. Chinese Journal of Public Health, 2009, 25(3): 300-302. DOI: 10.11847/zgggws2009-25-03-25

NAT2基因多态性与肝毒性巢式病例对照研究

Prospective nested case-control study on relation between N-acetyltransferase-2 acetylator phenotype and hepatotoxicity in China

  • 摘要: 目的 从分子流行病学水平探讨N-乙酰基转移酶-2(N-acetyltransferase,NAT2)基因多态性与抗结核药物引起肝毒性的关系,寻找抗结核药物引起肝毒性的易感基因。方法 选择符合条件的肺结核新发病例187例为研究队列,收集每个成员的相关信息并采静脉血3 ml,进行常规抗结核治疗。随访6个月,定期检测其肝功能,出现肝中毒症状的36人组成病例组,在未出现肝中毒症状的成员中抽取36例组成配对对照组,采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术检测其NAT2基因多态性。结果 经随访研究,因抗结核药引起的肝中毒患者占19.46%;1:1配对病例对照研究结果显示,慢型NAT2基因型肺结核患者较快型NAT2基因型的患者经抗结核药治疗后更易发生肝中毒(校正χ2=4.27,P<0.05),OR=4.00,95%CI=1.07~14.91。结论 慢型NAT2基因型是抗结核药物引起肝毒性的危险因素;通过检测肺结核病人的NAT2基因多态性,可指导其临床用药,有利于结核病的治疗。

     

    Abstract: Objective The aim of this study is to evaluate whe the rN-acety ltransferase-2 acetylator phenotype is associated with antituberculosis drug-induced hepatotoxicity in Chinese patients.Methods A total of 187 patients with newly diagnosed tuberculosis and antituberculosis treatment was followed prospectively for six months.The patients received liver function tests periodically.Patients(n=36)did not develop hepatotoxicity were selected to match each case,and their NAT2 genotypes were determined by the PCR-restriction fragment length polymorphism method.Results 19.46% of patients developed antitube rculosis drug-induced hepatotoxicity.There was a 4-fold risk of hepatotoxicity for the slow acetylators compared to the rapid acetylators(adjusted χ2=4.27,P<0.05;OR=4.00,95%CI=1.07-14.91).Conclusion Slow acetylator status of NAT2 was a significant susceptibility risk factor for antituberculosis drug-induced hepatototxicity and NAT2 genotyping may be a useful tool for predicting antituberculosis drug-induced hepatotoxicity.

     

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