CYP3A5*3和CYP3A4*18B基因多态性与抗结核药物性肝损伤的关系

郭桐君; 李玉红; 朱凌妍; 王悦; 田慎谦; 牛琛; 李艳辉; 任琦; 韩铁生; 冯福民

doi:10.16462/j.cnki.zhjbkz.2016.09.009

CYP3A53和CYP3A418B基因多态性与抗结核药物性肝损伤的关系

doi: 10.16462/j.cnki.zhjbkz.2016.09.009

华北理工大学公共卫生学院河北省煤矿卫生与安全重点实验室, 河北唐山 063000

基金项目:

唐山市重点实验室基金资助项目（08150201A-1-8）

详细信息

作者简介:
郭桐君(1990-),男,河北唐山人,在读硕士研究生。主要研究方向:传染病防治。

中图分类号: R394;R181
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出版历程
- 收稿日期: 2016-03-29
- 修回日期: 2016-08-09

Association between CYP3A53/CYP3A418-B gene polymorphisms and liver injury induced by anti-tuberculosis drugs

Hebei Province Key Laboratory of Occupational Health and Safety for Coal Idustry, School of Public Health, North China University of Science and Technology, Tangshan 063000, China

摘要

摘要: 目的探讨CYP3A5*3和CYP3A4*18B基因多态性与抗结核药物性肝损伤的关系。方法采用病例对照研究设计，发生肝损伤的患者中随机选取175例作为病例组，未发生肝损伤的患者中随机选取185例作为对照组，采用聚合酶链反应-限制性片段长度多态性技术检测研究对象CYP3A5*3、CYP3A4*18B基因多态性。结果 CYP3A5*3-6986A> G位点AA、AG、GG基因型在病例组和对照组频率分别为4.5%、38.9%、56.6%和16.7%、41.1%、42.2%；CYP3A4*18B-20232G> A位点GG、GA、AA基因型在病例组和对照组频率分别为42.3%、46.9%、10.8%和58.9%、34.1%、7.0%，组间差异均有统计学意义（均有P<0.05）。交互作用分析中CYP3A5*3（G）/CYP3A4*18B（G）、CYP3A5*3（G）/CYP3A4*18B（A）分别与CYP3A5*3（A）/CYP3A4*18B（G）比较，差异均有统计学意义（均有P<0.05）；CYP3A5*3（A）/CYP3A4*18B（A）与CYP3A5*3（A）/CYP3A4*18B（G）比较，差异无统计学意义（χ²=0.002，P=0.964）。结论 CYP3A5*3及CYP3A4*18B基因多态性与抗结核药物性肝损伤的发生均有关联；CYP3A5*3、CYP3A4*18B两个位点突变可能升高抗结核药物性肝损伤的发生风险，与均不突变相比，CYP3A5*3单一突变也可能升高抗结核药物性肝损伤发生的风险。
- 抗结核药 /
- 肝 /
- 多态性,单核苷酸
Abstract: Objective To explore the association between the gene polymorphisms of cytochrome CYP3A5*3,CYP3A4*18B and anti-tuberculosis drug-induced liver injury. Methods A case-control study was conducted. 175 Chinese patients with ADLI were selected from the patients who received the anti-tuberculosis therapy as the ADLI group and 185 patients who had not have a hepatic injury were selected as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify the genotypes of CYP3A5*3 gene and CYP3A4*18B gene. Results The frequency of A/G of CYP3A5*3-6986 and the frequency of G/A of CYP3A4*18B-20232G were 4.5%,38.9%,56.6% and 42.3%,46.9%,10.8% respectively in cases and 16.7%,41.1%,42.2% and 58.9%, 34.1%, 7.0% in controls. There were differences of genetic polymorphisms between CYP3A5*3 and CYP3A4*18B in the two groups(all P< 0.05). The frequency of the combination of CYP3A5*3(G)/CYP3A4*18B(G)and CYP3A5*3(G)/CYP3A4*18B(A)between the case group and the control group had statistically difference(all P<0.05)when compared with CYP3A5*3(A)/CYP3A4*18B(G). The frequency of the combination of CYP3A5*3(A)/CYP3A4*18B(A)between the case group and the control group had no statistically difference(χ²=0.002,P=0.964)when compared with CYP3A5*3(A)/CYP3A4*18B(G). Conclusions The CYP3A5*3 and CYP3A4*18B genetic polymorphisms will raise the risk of liver injury induced by anti-tuberculosis drugs,and the variation combination of CYP3A5*3 and CYP3A4*18B will add to the risk to ADLI. The variation combination of CYP3A5*3(G)/CYP3A4*18B(G) will raise the risk of ADLI compared with CYP3A5*3(A)/CYP3A4*18B(G).
- Anti-tuberculosis drugs /
- Liver /
- Polymorphism, single nucleotide

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