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首页> 外文期刊>Clinical & 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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摘要

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之间有很强的联系。建议在某些人群中在处方别嘌呤醇之前筛查HLA-B〜(?)58?:?01等位基因。已经发现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,并且这些SNP被提议作为HLA-B〜(β)58β:α01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之间的关系。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〜(?)58?:?01等位基因没有完美的联系。 。使用这些SNP作为HLA-B〜(?)58?:?01等位基因的替代标记进行筛选以避免在别嘌呤醇给药之前发生SCAR,因为它们与HLA-B〜(?)58?:?01的连接不完善,因此需要谨慎。等位基因。

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