{"_":"斯洛文尼亚人群的基因图谱分析。","i":["NUDT15"]}

摘要(中文译文)

确定变异等位基因以预测患者对硫嘌呤治疗的反应，是药物基因组学在临床实践中最先成功应用的范例之一。然而，尽管根据基因型调整了硫嘌呤剂量，一些野生型患者在接受标准剂量时仍表现出毒性。在过去十年中，药物基因NUDT15已成为硫嘌呤治疗的重要协同调节因子。最初，NUDT15被认为主要在亚洲人群中具有重要意义，但近期研究也强调了其在欧洲人群中的相关性。为评估NUDT15在斯洛文尼亚人群中的药物遗传学意义，我们对109名健康个体和37名急性淋巴细胞白血病患者的外显子1和外显子3的扩展区域进行了测序。我们鉴定出8个变异，包括1个已确立临床意义的变异（等位基因*3）和1个极为罕见的变异（Chr13位于48045861；GRCh38，NC_000013.11）。大多数先前描述的变异在一般人群和ALL队列中的频率与其他欧洲人群的报道一致，但rs45465203除外，该变异在斯洛文尼亚人群中频率较低。除NUDT15外，没有任何变异与ALL患者的累积硫嘌呤剂量相关。然而，这些变异值得在更大的ALL队列中进一步研究。

Abstract

Determining variant alleles to predict patient response to thiopurine therapy represents one of the first successful implementations of pharmacogenomics in clinical practice. However, despite the -adjusted thiopurine dosing, some wild-type patients still exhibit toxicity at standard doses. Over the past decade, the pharmacogene has emerged as a significant co-modulator of thiopurine therapy. Initially, was considered important predominantly in Asian populations, but recent studies have highlighted its relevance in European populations as well.To evaluate the pharmacogenetic significance of in the Slovenian population, we sequenced extended regions of exon 1 and exon 3 in 109 healthy individuals and 37 patients with acute lymphoblastic leukemia.We identified eight variants, including one with established clinical significance (allele *3) and one extremely rare variant (Chr13 at 48045861; GRCh38, NC_000013.11). The frequencies of most previously described variants in both the general population and in the ALL cohort were consistent with those reported in other European populations, except for rs45465203, which was less frequent in the Slovenian population. None of the variants, except for , were associated with cumulative thiopurine doses in ALL patients. However, these variants warrant further investigation in larger ALL cohorts.

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