The Pharmacogenomic HLA Biomarker Associated to Adverse Abacavir Reactions: Comparative Analysis of Different Genotyping Methods
The Pharmacogenomic HLA Biomarker Associated to Adverse Abacavir Reactions: Comparative Analysis of Different Genotyping Methods
复制标题
DOI：
10.2174/138920212800793311
复制
发表时间：
2012-06-01
期刊：
影响因子：
2.6
通讯作者：
Giardina, Emiliano
中科院分区：
文献类型：
--
作者：
Stocchi, Laura;Cascella, Raffaella;Giardina, Emiliano
许多药物基因组生物标志物（PGBM）被确定并转化为临床实践，通过标签更新影响药物的使用。在这种情况下，阿巴卡韦是药物遗传学研究转化为临床实践的最杰出的例子之一。药物遗传学研究表明，阿巴卡韦HSRs与主要组织相容性复合物i类高度相关。大型研究证实了前瞻性HLA-B*57:01筛选预防阿巴卡韦HSRs的有效性。根据这些结果，阿巴卡韦的标签已经进行了修改：欧洲药品管理局（EMA）和FDA建议/建议阿巴卡韦在给药之前必须进行特定的基因分型测试。HLA位点具有高度多态性，存在许多密切相关的等位基因，这使得HLA- b *57:01与其他相关等位基因的区分变得困难，近年来已经开发了许多不同的分子技术来检测HLA- b *57:01的存在。在这篇综述中，我们总结了实验室用于HLA-B*57:01基因分型的现有技术，概述了科学和药物经济学的利弊。
Many pharmacogenomic biomarkers (PGBM) were identified and translated into clinical practice, affecting the usage of drugs via label updates. In this context, abacavir is one of the most brilliant examples of pharmacogenetic studies translated into clinical practice. Pharmacogenetic studies have revealed that abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir. Accordingly to these results the abacavir label has been modified: the European Medicines Agency (EMA) and the FDA recommend/suggested that the administration of abacavir must be preceded by a specific genotyping test. The HLA locus is extremely polymorphic, exhibiting many closely related alleles, making it difficult to discriminate HLA-B*57:01 from other related alleles, and a number of different molecular techniques have been developed recently to detect the presence of HLA-B*57:01. In this review, we provide a summary of the available techniques used by laboratories to genotype HLA-B*57:01, outlining the scientific and pharmacoeconomics pros and cons.