抗癫痫药物致皮肤型药物不良反应与HLA基因关系的研究进展

Progress of the Research of the Relationship Between Antiepileptic Drug-induced Cutaneous Adverse Drug Reactions and HLA Genes Polypeptide

为了解近年来芳香族抗癫痫药物致皮肤型不良反应（cADRs）与各国不同人群、种族中HLA基因多态性之间的关系，为抗癫痫药物合理应用和风险管理实施个体化治疗提供信息服务，本文通过8个主要关键词联机检索2004～2013年全球发表的英文及中文文献。通过纳入排除标准后提取出密切相关文献32篇。对这些异质性论文报告的研究结果进行汇总分析，系统综述相关领域的研究进展。研究发现，对亚洲、欧洲地区人群HLA基因与抗癫痫药物致cADRs相关性：①HLA-B＊1502基因在亚洲部分地区及汉族人群中（除日本、韩国外）与CBZ-cADRs中的SJS/TEN强相关，与CBZ HSS/MPE无相关性；②HLA-B＊1502基因与其他芳香族AEDs导致的SJS/TEN的关系不确定；③HLA-B＊1511基因与日本、韩国人群CBZ SJS/TEN的发生有一定联系；④HLA-A＊3101基因与欧洲、日本、韩国人群中CBZ导致各种类型的cADRs密切相关；⑤在不同人群、种族中进行HLA-B＊1502基因筛查其意义及成本效益分析存在差异；⑥HLA-B＊1502基因在严重皮肤不良反应的药理作用机制仍不明确。表明对亚裔人（除外日本、韩国）使用CBZ治疗前需要进行HLA-B＊1502基因筛查，而对日本、韩国人需要检测HLA-B＊1511基因，能有效避免在使用CBZ过程中发生严重药物不良反应，规避CBZ的用药风险，杜绝经济损失。

This article aims to review the relationship between aromatic antiepileptic drugs （AEDs） induced cutaneous adverse drug reactions （cADRs） and HLA genes polypeptide in different national or ethnic groups to provide an information service for the rational use, risk management and individualized medication of AEDs. Through the inclusion and exclusion criteria, 32 closely related articles published during year 2004 2013 in English and Chinese were collected by the online search through 8 key words. The findings of these studies with heterogeneity were pooled and analyzed and the advances of researches in related field were systematically reviewed. The studies found the relativity between Asian, European HLA genes with AEDs induced cADRs： 1.HLA-B＊1502 gene in parts of Asia and the Han population （ except in Japan, Korea ） was strongly correlated with SJS/TEN which belonged to carbamazepine （CBZ）-cADRs, but not correlated with CBZ-HSS/MPE; 2. The relationship between HLA-B＊1502 gene and other aromatic AEDs causing SJS/TEN was uncertain; 3.HLA-B＊1511 gene had some relation with CBZ SJS/TEN occurrence in Japanese and Korean people; 4.HLA-A＊3101 gene and various types of CBZ induced cADRs in Europe, Japan, South Korea were closely related; 5.Cost benefit analysis of HLA-B＊1502 genetic screening were different from disparate populations and races; 6. The pharmacological mechanism of HLA-B＊1502 gene in severe cADRs remained unclear. As a conclusion , before treatment with CBZ, Asians （except Japan, Korea） required HLA-B＊1502 genetic screening, while the Japanese, Koreans needed to detect their HLA-B＊1511 gene. This way, serious ADRs could be effectively avoided in using CBZ and risks of its medication and economic losses could be prevented .