HLA-B基因多态性与抗癫痫药拉莫三嗪致皮肤不良反应关系的meta分析

李堂雪; 李会婷; 吴妍; 汪电雷; 史天陆<sup>*</sup>

引用本文:	李堂雪,李会婷,吴妍,汪电雷,史天陆.HLA-B基因多态性与抗癫痫药拉莫三嗪致皮肤不良反应关系的meta分析[J].中国现代应用药学,2024,41(1):126-132.
	LI Tangxue,LI Huiting,WU Yan,WANG Dianlei,SHI Tianlu.Meta-analysis of Association Between HLA-B Gene Polymorphism and Antiepileptic Lamotrigine-induced Cutaneous Adverse Drug Reactions[J].Chin J Mod Appl Pharm(中国现代应用药学),2024,41(1):126-132.

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HLA-B基因多态性与抗癫痫药拉莫三嗪致皮肤不良反应关系的meta分析
李堂雪¹, 李会婷², 吴妍², 汪电雷¹, 史天陆^1,2
1.安徽中医药大学药学院，合肥 230012;2.中国科学技术大学附属第一医院(安徽省立医院)药学部，合肥 230001

摘要:

目的系统评价人类白细胞抗原B(human leukocyte antigen B，HLA-B)基因多态性与抗癫痫药拉莫三嗪致皮肤不良反应(lamotrigine-cutaneous adverse reactions，LTG-cADRs)的相关性。方法通过计算机全面检索中国期刊全文数据库、万方数字化期刊全文库、中国科技期刊全文数据库、PubMed、Web of Science、Science Direct数据库，检索时间截至2022年7月15日，采用RevMan5.4软件进行meta分析。结果共纳入16篇病例对照研究，331例LTG-cADRs癫痫患者，其中94例拉莫三嗪致史-约综合征/中毒性表皮坏死松懈症(lamotrigine-Stevens-Johnson syndrome/toxic epidermal necrolysis，LTG-SJS/TEN)患者，232例拉莫三嗪致斑丘疹(lamotrigine-maculopapule，LTG-MPE)患者，5例伴嗜酸粒细胞增多和系统症状的药疹(lamotrigine-drug rash with eosinophilia and systemic symptoms，LTG-DRESS)患者；612例拉莫三嗪耐受癫痫患者。Meta分析结果显示：HLA-B*1502等位基因与LTG-SJS/TEN存在显著相关性(OR=3.03，95%CI：1.70~5.39，P=0.000 2)。HLA-B*1502、HLA-B*5801、HLA-B*1302等位基因均与LTG-MPE无显著相关性。结论 HLA-B*1502等位基因与LTG-SJS/TEN存在相关性，可能是LTG-SJS/TEN风险基因；HLA-B*1502、HLA-B*5801和HLA-B*1302等位基因与LTG-MPE无相关性。

关键词: HLA-B 拉莫三嗪皮肤不良反应癫痫 meta分析

DOI：10.13748/j.cnki.issn1007-7693.20223831

分类号:R969.3

基金项目:安徽省质量基础设施标准化专项(2022MKS06)；安徽省高校自然科学研究项目(2023AH040397)

Meta-analysis of Association Between HLA-B Gene Polymorphism and Antiepileptic Lamotrigine-induced Cutaneous Adverse Drug Reactions

LI Tangxue¹, LI Huiting², WU Yan², WANG Dianlei¹, SHI Tianlu^1,2

1.School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China;2.Department of Pharmacy, the First Affiliated Hospital of University of Science and Technology of China, Anhui Provincial Hospital, Hefei 230001, China

Abstract:

OBJECTIVE To systematically evaluate the association between human leukocyte antigen B(HLA-B) gene polymorphisms and lamotrigine-induced cutaneous adverse drug reactions(LTG-cADRs). METHODS CNKI, Wanfang Data, VIP, PubMed, Web of Science, Science Direct were comprehensively searched from the inception to July 15, 2022. The software RevMan 5.4 was used for the meta-analysis. RESULTS A total of 16 case-control studies were included, 331 patients with LTG-cADRs epilepsy, including 94 lamotrigine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis(LTG-SJS/TEN) patients, 232 lamotrigine-maculopapule(LTG-MPE) patients and 5 lamotrigine- drug rash with eosinophilia and systemic symptoms(LTG-DRESS) patients; 612 lamotrigine-tolerant patients. Meta-analysis results showed that the HLA-B*1502 allele was significantly associated with LTG-SJS/TEN(OR=3.03, 95%CI: 1.70−5.39, P=0.000 2). The HLA-B*1502, HLA-B*5801, HLA-B*1302 alleles were not significantly associated with LTG-MPE. CONCLUSION HLA-B*1502 allele is associated with LTG-SJS/TEN, which may be a risk gene for LTG-SJS/TEN. HLA-B*1502, HLA-B*5801, HLA-B*1302 are not associated with LTG-MPE.

Key words: HLA-B lamotrigine cutaneous adverse drug reactions epilepsy meta-analysis