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  

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

作　　者：李堂雪 李会婷 吴妍[2] 汪电雷 史天陆 LI Tangxue;LI Huiting;WU Yan;WANG Dianlei;SHI Tianlu(School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;Department of Pharmacy,the First Affiliated Hospital of University of Science and Technology of China,Anhui Provincial Hospital,Hefei 230001,China)

机构地区：[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

出　　处：《中国现代应用药学》2024年第1期126-132,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：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)。

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=0.0002)。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。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 LTGcADRs 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(LTGDRESS) 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.

关 键 词：HLA-B 拉莫三嗪 皮肤不良反应 癫痫 META分析 

分 类 号：R969.3[医药卫生—药理学]