HLA基因多态性与药物性肝损伤的关系

王露媛; 姜敏杰; 高普均

doi:10.3969/j.issn.1001-5256.2021.02.048

HLA基因多态性与药物性肝损伤的关系

DOI: 10.3969/j.issn.1001-5256.2021.02.048

吉林大学第一医院肝胆胰内科，长春 130021

基金项目:

“艾滋病和病毒性肝炎等重大传染病防治”国家科技重大专项 (2017ZX10202202);

“艾滋病和病毒性肝炎等重大传染病防治”国家科技重大专项 (2018ZX10302206);

“艾滋病和病毒性肝炎等重大传染病防治”国家科技重大专项 (2018ZX10723203);

国家重点研发计划“精准医学研究”专项 (2017YFC0908103);

吉林省自然科学基金 (2018SCZWSZX-003);

吉林省自然科学基金 (JLSCZD2019-008);

吉林大学高层次创新团队建设项目 (2017TD-08);

中央高校基本科研业务费专项资金

作者贡献声明：王露媛、高普均负责拟定写作思路；王露媛、姜敏杰负责检索文献，资料分析，参与收集数据；王露媛负责撰写文章；高普均负责指导撰写文章并最后定稿。

详细信息

作者简介:
王露媛(1993—)，男，主要从事肝脏疾病的临床研究

通信作者:
高普均，gpj0411@163.com

中图分类号: R575
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出版历程
- 收稿日期: 2020-08-08
- 录用日期: 2020-10-19
- 出版日期: 2021-02-20

Association between human leukocyte antigen gene polymorphism and drug-induced liver injury

Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, China

Research funding:

(2017ZX10202202);

(2018ZX10302206);

(2018ZX10723203);

(2017YFC0908103);

(2018SCZWSZX-003);

(JLSCZD2019-008);

(2017TD-08);

摘要

摘要: 药物性肝损伤是临床常见的药物不良反应之一，其临床诊治极为困难，且易发展成急性肝衰竭。相关药物基因组学研究已发现人类白细胞抗原(HLA)基因与药物性肝损伤之间有很强的遗传相关性。综述了药物性肝损伤的HLA基因多态性研究进展，以期揭示免疫因素在药物性肝损伤发生机制中的作用，发现相应基因生物标志物，提高临床用药的安全性。
- 化学性与药物性肝损伤 /
- HLA抗原 /
- 多态性, 单核苷酸
Abstract: Drug-induced liver injury (DILI) is one of the common adverse drug reactions in clinical practice, and it is difficult to diagnose and treat and may easily develop into acute liver failure. Related pharmacogenomics studies have found a strong genetic correlation between human leukocyte antigen (HLA) genes and DILI. This article reviews the research advances in HLA gene polymorphism in DILI, in order to reveal the role of immune factors in the pathogenesis of DILI, identify related genetic biomarkers, and improve the safety of clinical medication.
- Chemical and Drug Induced Liver Injury /
- HLA Antigens /
- Polymorphism, Single Nucleotide

HTML全文

表 1 HLA基因多态性与常见DILI的相关性

药物	HLA基因	人群	OR	参考文献
阿莫西林-克拉维酸	DRB1^*15:01	苏格兰	9.25	[12]
阿莫西林-克拉维酸	DRB1^15:01-DQB1^06:02	欧洲	3.3	[7]
阿莫西林-克拉维酸	A^*02:01	欧洲	2.2	[7]
氟氯西林	B^*57:01	英国	80.6	[8]
米诺环素	A^*35:02	高加索	29.6	[6]
甲氧苄啶-磺胺甲噁唑	B^*14:01	欧翳美国人	9.2	[32]
甲氧苄啶-磺胺甲噁唑	B^*35:01	非翳美国人	-	[32]
希美加群	DRB1^07-DQA1^02	英国	4.4	[18]
拉帕替尼	DRB1^*07:01	高加索	6.9~14.1	[34-35]
拉帕替尼	DRA1^*02:01	高加索	9.0~14.1	[34-35]
帕唑帕尼	B^*57:01	全球	-	[36]
何首乌	B^*35:01	中国	86.5¹⁾	[43]
何首乌	B^*35:01	中国	143.9²⁾	[43]
卡马西平	A^*31:01	欧洲	7.3	[39]
英夫利昔单抗	B^*39:01	欧洲	43.6	[44]
氟吡汀	DRB1^16:01-DQB1^05:02	德国	18.7	[38]
注：1)治疗对照组；2)人群对照组。

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