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HLA 与药物不良反应的关联。

HLA Association with Drug-Induced Adverse Reactions.

机构信息

Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan.

Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taipei, Taiwan.

出版信息

J Immunol Res. 2017;2017:3186328. doi: 10.1155/2017/3186328. Epub 2017 Nov 23.

Abstract

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of gene (terms ). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: and . In addition, allele was reported to be related to carbamazepine-induced SJS/TEN, and in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs.

摘要

药物不良反应(ADR)仍然是医疗保健中的一个常见且主要的问题。严重的皮肤药物不良反应(SCAR),如史蒂文斯-约翰逊综合征(SJS)/中毒性表皮坏死松解症(TEN),死亡率范围为 10%至 30%以上,可能危及生命。最近的一些研究表明,ADR 具有很强的遗传易感性。一些药物引起的 ADR 与人类白细胞抗原(HLA)基因的特定等位基因有显著关联。例如,对用于治疗人类免疫缺陷病毒(HIV)感染的药物阿巴卡韦的过敏反应已被证明与基因(术语)的等位基因 57:01 有关。由于不同种族人群中的等位基因频率不同,与其他人群相比,高加索人群中阿巴卡韦过敏反应的发生率要高得多。抗甲状腺药物(ATD)引起的粒细胞缺乏症与两个等位基因强烈相关:和。此外,据报道,等位基因与卡马西平引起的 SJS/TEN 以及阿巴卡韦过敏反应和氟氯西林引起的药物性肝损伤(DILI)有关。在这篇综述中,我们总结了与不同药物引起的 ADR 相关的 HLA 基因等位基因。

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