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首页> 外文期刊>Clinical and Translational Allergy >Evaluation of a pharmacogenetic test in Thailand for abacavir hypersensitivity screening in human immunodeficiency virus infection
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Evaluation of a pharmacogenetic test in Thailand for abacavir hypersensitivity screening in human immunodeficiency virus infection

机译：在泰国进行药物遗传学测试以评估人类免疫缺陷病毒感染中的阿巴卡韦超敏反应

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Abacavir hypersensitivity reaction (ABC-HSR) is associatedwith the presence of HLA-B*5701 allele. Alternativetests for ABC-HSR associated allele determination areneeded where sequence-based HLA typing is not available,particularly in resource-limited settings or developingcountries. This study focused on the development andevaluation of two HLA-B*5701 tagging SNPs (singlenucleotide polymorphism) HCP5 (HLA complex P5)rs2395029 and TNF (tumor necrosis factor) rs3093726genotyping assays. Two hundred and thirteen purifiedgenomic DNA samples were used to evaluate the performancecharacteristics of a HLA-B*5701 screening methodbased on allele-specific polymerase chain reaction(AS-PCR) with melting curve analysis. HCP5 rs2395029and TNF rs3093726 were also genotyped using simpleprobe real-time PCR assay. All samples were successfullygenotyped wherein AS-PCR genotyping provided 100%sensitivity, specificity, positive predictive value (PPV) andnegative predictive value (NPV) when compared withspecific HLA-B status by sequencing based assay. Whencomparing the AS-PCR screening method with the HCP5rs2395029 and TNF rs3093726 genotyping method, theformer had 100% sensitivity, 100% specificity, 100% PPVand 100% NPV using a simple probe; while the latter onehad 95.24% sensitivity, 100% specificity, 100% PPV and99.48% NPV, respectively. In conclusion, our study lendssupport on a molecular tool for pharmacogeneticscreening in resource-limited settings. Thus, serious drughypersensitivity associated with ABC may potentially bereduced in Thailand by further evaluation of the proposedassay in clinical practice.
机译：阿巴卡韦超敏反应（ABC-HSR）与HLA-B * 5701等位基因的存在有关。在基于序列的HLA分型不可用的地方，尤其是在资源有限的国家或发展中国家，需要ABC-HSR相关等位基因测定的替代测试。这项研究的重点是两个HLA-B * 5701标签SNP（单核苷酸多态性）HCP5（HLA复合物P5）rs2395029和TNF（肿瘤坏死因子）rs3093726基因分型分析的开发和评估。 213个纯化的基因组DNA样品被用于评估基于等位基因特异性聚合酶链反应（AS-PCR）和熔解曲线分析的HLA-B * 5701筛选方法的性能特征。 HCP5 rs2395029和TNF rs3093726也使用简单探针实时PCR分析进行基因分型。通过基于测序的检测与所有HLA-B状态相比，所有样品均成功进行了基因分型，其中AS-PCR基因分型提供了100％的敏感性，特异性，阳性预测值（PPV）和阴性预测值（NPV）。当将AS-PCR筛选方法与HCP5rs2395029和TNF rs3093726基因分型方法进行比较时，使用简单的探针，前者的敏感性为100％，特异性为100％，PPV为100％，NPV为100％。后者的灵敏度分别为95.24％，特异性100％，PPV 100％和NPV99.48％。总之，我们的研究为在资源有限的环境中进行药物遗传学筛选的分子工具提供了支持。因此，通过在临床实践中进一步评估拟议的测定方法，泰国可能会降低与ABC相关的严重的药物超敏性。

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