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

陈茹; 王晶; 唐少文; 吕晓珍; 张渊; 武珊珊; 夏愔愔; 詹思延

文章摘要

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].中华流行病学杂志,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

收稿日期:2016-03-02 出版日期:2016-07-15

DOI：10.3760/cma.j.issn.0254-6450.2016.07.004

中文关键词: 抗结核药物药物性肝损害易感基因基因多态性

英文关键词: Anti-tuberculosis drug Drug-induced liver injury Susceptibility gene Gene polymorphism

基金项目:国家自然科学基金（81072387，81473067）；北京市自然科学基金（7111006）

作者	单位	E-mail
陈茹	100191 北京大学公共卫生学院流行病与卫生统计学系
王晶	3010 墨尔本, 澳大利亚墨尔本大学儿科系, 默多克儿童研究中心
唐少文	211166 南京医科大学公共卫生学院流行病学系
吕晓珍	100191 北京大学精神卫生研究所临床研究室
张渊	L8S4K1 汉密尔顿, 加拿大麦克马斯特大学临床流行病与卫生统计学系
武珊珊	100050 北京, 首都医科大学附属北京友谊医院, 国家消化中心
夏愔愔	102206 北京, 中国疾病预防控制中心结核病控制中心
詹思延	100191 北京大学公共卫生学院流行病与卫生统计学系	siyan-zhan@bjmu.edu.cn

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中文摘要:

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。

英文摘要:

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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