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首页> 美国卫生研究院文献>Clinical and Developmental Immunology >Comparison between the HLA-B∗58 : 01 Allele and Single-Nucleotide Polymorphisms in Chromosome 6 for Prediction of Allopurinol-Induced Severe Cutaneous Adverse Reactions
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Comparison between the HLA-B∗58 : 01 Allele and Single-Nucleotide Polymorphisms in Chromosome 6 for Prediction of Allopurinol-Induced Severe Cutaneous Adverse Reactions

机译：比较HLA-B * 58：01等位基因和6号染色体单核苷酸多态性对别嘌醇引起的严重皮肤不良反应的预测

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Severe cutaneous adverse drug reactions (SCARs) are life-threatening reactions. The strong association between the HLA-B∗58 : 01 allele and allopurinol-induced SCARs is well recognized. Screening for HLA-B∗58 : 01 allele before prescribing allopurinol in some populations has been recommended. Several single-nucleotide polymorphisms (SNPs) in chromosome 6 have been found to be tightly linked with the HLA allele, and these SNPs have been proposed as surrogate markers of the HLA-B∗58 : 01 allele. This study aimed to evaluate the association between three SNPs in chromosome 6 and allopurinol-induced SCARs in a Thai population. The linkage disequilibrium between the HLA-B∗58 : 01 allele and these SNPs was also evaluated. Results showed that three SNPs including rs9263726, rs2734583, and rs3099844 were significantly associated with allopurinol-induced SCARs but with a lower degree of association when compared with the HLA-B∗58 : 01 allele. The sensitivity, specificity, PPV, and NPV of these SNPs were comparable to those of the HLA-B∗58 : 01 allele. Although detection of the SNP is simpler and less expensive compared with that of the HLA-B∗58 : 01 allele, these SNPs were not perfectly linked with the HLA-B∗58 : 01 allele. Screening using these SNPs as surrogate markers of the HLA-B∗58 : 01 allele to avoid SCARs prior to allopurinol administration needs caution because of their imperfect linkage with the HLA-B∗58 : 01 allele.
机译：严重的皮肤不良药物反应（SCAR）是威胁生命的反应。 HLA-B ∗ 58：01等位基因与别嘌呤醇诱导的SCAR之间存在很强的联系。建议在某些人群中在处方别嘌呤醇之前先筛选HLA-B ∗ 58：01等位基因。已发现6号染色体上的几个单核苷酸多态性（SNP）与HLA等位基因紧密相连，这些SNP被提议作为HLA-B ∗ 58：01等位基因的替代标记。这项研究旨在评估泰国人群中第6号染色体上的三个SNP与别嘌呤醇诱导的SCAR之间的关联。还评估了HLA-B ∗ 58：01等位基因与这些SNP之间的连锁不平衡。结果显示，rs9263726，rs2734583和rs3099844这三个SNP与别嘌呤醇诱导的SCAR显着相关，但与HLA-B ∗ 58：01等位基因相比，其缔合度较低。这些SNP的敏感性，特异性，PPV和NPV与HLA-B ∗ 58：01等位基因相当。尽管与HLA-B * 58：01等位基因相比，SNP的检测更简单且成本更低，但这些SNP与HLA-B * 的关联并不完美 58：01 等位基因。使用这些SNP作为 HLA-B ∗ 58：01 等位基因的替代标记进行筛查以避免在别嘌呤醇给药前发生SCAR，因为它们与 HLA-B ∗ 58：01 等位基因的连接不完美。

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