| 陈茹,王晶,唐少文,吕晓珍,张渊,武珊珊,夏愔愔,詹思延.抗结核治疗队列人群药物性肝损害的易感基因多态性研究[J].Chinese journal of Epidemiology,2016,37(7):925-929 |
| 抗结核治疗队列人群药物性肝损害的易感基因多态性研究 |
| Study on polymorphisms of genes with susceptibility to drug induced liver injury in a cohort receiving anti-tuberculosis treatment |
| Received:March 02, 2016 |
| DOI：10.3760/cma.j.issn.0254-6450.2016.07.004 |
| KeyWord: 抗结核药物 药物性肝损害 易感基因 基因多态性 |
| English Key Word: Anti-tuberculosis drug Drug-induced liver injury Susceptibility gene Gene polymorphism |
| FundProject:国家自然科学基金（81072387，81473067）；北京市自然科学基金（7111006） |
| Author Name | Affiliation | E-mail | | Chen Ru | Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China | | | Wang Jing | Department of Paediatrics, The University of Melbourne, and Murdoch Children Research Institute, Melbourne 3010, Australia | | | Tang Shaowen | Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, China | | | Lyu Xiaozhen | Clinical Research Division, Peking University Institute of Mental Health, Beijing 100191, China | | | Zhang Yuan | Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton L8 S4 K1, Canada | | | Wu Shanshan | Beijing Friendship Hospital, Capital Medical University, and National Clinical Research Center of Digestive Diseases, Beijing 100050, China | | | Xia Yinyin | Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China | | | Zhan Siyan | Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China | siyan-zhan@bjmu.edu.cn |
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| Abstract: |
| 目的 探索药物代谢、转运和免疫反应基因多态性与中国人群抗结核药致肝损害的关联。方法 利用“中国结核病防治规划抗结核病药品不良反应研究”的人群资料和样本，构建1：4巢式病例对照研究，选择与抗结核药物所致肝损害相关的三相代谢基因以及相关免疫基因，采用TaqMan分型技术检测基因单核苷酸多态性（SNP），结合Lasso回归和多因素条件logistic回归筛选易感基因。结果 共检测33个基因的75个SNP位点，Lasso回归和logistic回归的合并分析显示，SLCO1B1 rs4149014、HSPA1L rs2227956、STAT3 rs1053023和IL-6 rs2066992基因多态性与抗结核药致肝损害的关联有统计学意义（P<0.05）。结论 SLCO1B1、HSPA1L、STAT3和IL-6 基因可能是抗结核治疗人群发生药物性肝损害的易感基因。 |
| English Abstract: |
| Objective To investigate the association between the polymorphisms of genes involving in drug metabolism and transport as well as immunological reaction and the risk of anti-tuberculosis drug-induced liver injury (ATLI) in Chinese. Methods This 1:4 matched case-control study was conducted by using the data from a cohort study of Anti-tuberculosis Drugs Induced Adverse Reactions in National Tuberculosis Prevention and Control Progtam of China. Genes involving in three phase of drug metabolism and transport as well as related immunological reaction were chosen and single nucleotide polymorphisms (SNPs) were genotyped by TaqMan allele discrimination technology. Lasso regression and multivariate conditional logistic regression analysis were used to select susceptible genes. Results A total of 33 genes with 75 SNPs were tested. The combined results of Lasso and regression logistic regression analysis showed that genetic polymorphism of SLCO1B1 rs4149014, HSPA1L rs2227956, STAT3 rs1053023 and IL-6 rs2066992 were significantly associated with the risk of ATLI (P<0.05). Conclusion SLCO1B1, HSPA1L, STAT3 and IL-6 might be the susceptibility genes of drug induced liver injury in patients receiving anti-tuberculosis treatment. |
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