Human leukocyte antigen (HLA) and pharmacogenetics: screening for HLA-B*57:01 among human immunodeficiency virus-positive patients from southern Alberta
Human leukocyte antigen (HLA) and pharmacogenetics: screening for HLA-B*57:01 among human immunodeficiency virus-positive patients from southern Alberta
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DOI：
10.1016/j.humimm.2011.12.002
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发表时间：
2012-02-01
期刊：
影响因子：
2.7
通讯作者：
Khan, Faisal M.
中科院分区：
文献类型：
--
作者：
Berka, Noureddine;Gill, John M.;Khan, Faisal M.
人类白细胞抗原（HLA）在药物不良反应（ADR）中的作用越来越受到药物遗传学领域的关注。在这里，我们报告了一项回顾性分析的关联HLA-B*5701与阿巴卡韦过敏综合征（AHS）在一个大型的加拿大队列的489人免疫缺陷病毒-1阳性患者暴露于阿巴卡韦。共有3.7%的阿巴卡韦暴露患者发生了AHS。使用聚合酶链反应序列特异性引物基因分型，HLA-B*5701等位基因在20例（4.1%）中观察到。在20例HLA-B*5701（+）阿巴卡韦治疗的患者中，18例（90%）发生了AHS。HLA-B*5701等位基因的携带表明与阿巴卡韦超敏反应密切相关（p < 0.0001;比值比= 6,934; 95%置信区间= 321- 149735）。HLA-B*5701基因分型具有较高的敏感性、特异性、阳性预测值和阴性预测值。来自该研究的数据强调了组织相容性和免疫遗传学实验室在绘制其他与ADR相关的特征较少的HLA和免疫遗传学标记方面的重要性。版权所有（C）2012由Elsevier Inc.发布。美国组织相容性和免疫遗传学学会（American Society for Histocompatibility and Immunogenetics）All rights reserved.
The field of pharmacogenetics is witnessing a growing interest in the role of the human leukocyte antigen (HLA) in manifestation of adverse drug reactions (ADR). Here we report a retrospective analysis of the association of HLA-B*5701 with abacavir hypersensitivity syndrome (AHS) in a large Canadian cohort of 489 human immunodeficiency virus-1-positive patients exposed to abacavir. A total of 3.7% of abacavir-exposed patients had developed AHS. Using polymerase chain reaction sequence-specific primer-based genotyping, the HLA-B*5701 allele was observed in 20 patients (4.1%). Of the 20 HLA-B*5701(+) abacavir-treated patients, 18(90%) had developed AHS. Carriage of the HLA-B*5701 allele indicated a strong association with abacavir hypersensitivity (p < 0.0001; odds ratio = 6,934; 95% confidence interval = 321-149,735). HLA-B*5701 genotyping demonstrated high sensitivity, specificity, and positive and negative predictive values. The data derived from the study highlight the importance of engaging histocompatibility and immunogenetics laboratories in taking a lead in mapping other less characterized HLA and immunogenetic markers associated with ADRs. Crown copyright (C) 2012 Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. All rights reserved.