NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia
NUDT15 gene polymorphism related to mercaptopurine intolerance in Taiwan Chinese children with acute lymphoblastic leukemia
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DOI：
10.1038/tpj.2015.75
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发表时间：
2016-11-01
影响因子：
2.8
通讯作者：
Shih, L-Y
中科院分区：
文献类型：
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作者：
Liang, D-C;Yang, C-P;Shih, L-Y
最近的一项研究发现，韩国克罗恩病患者的NUDT15基因（rs116855232 C > T）变异与硫嘌呤不耐受相关。这项研究促使我们在台湾人群中证实这一发现。对144例急性淋巴细胞白血病（ALL）患儿和100例骨髓正常的慢性免疫性血小板减少性紫癜或局限性淋巴瘤患者进行了检查。采用两种候选基因方法，分别为NUDT15的pyrosequencing和TaqMan法进行硫嘌呤甲基转移酶（TPMT）基因分型（rs1142345 A > G）。我们发现在ALL患儿中NUDT15的风险等位基因频率为11.6%，在成人中为15.5%。相比之下，TPMT的风险等位基因频率在ALL患儿中仅为1.6%，在成人中为0.5%。与欧洲血统相比，NUDT15风险变异的高频率与台湾ALL儿童巯基嘌呤不耐受密切相关，而TPMT风险变异的低频率与此密切相关。在NUDT15多态性方面，纯合子组、杂合子组和野生型组巯基嘌呤的最大耐受日剂量分别为9.4 mgm（-2）、30.7 mgm（-2）和44.1 mgm（-2）。不同基因型的结果无显著差异。
A recent study identified a variant of the NUDT15 gene (rs116855232 C > T) associated with intolerance to thiopurine in Korean patients with Crohn's disease. This study prompted us to substantiate the finding in a Taiwanese population. Four hundred and four children with acute lymphoblastic leukemia (ALL), and 100 adults with chronic immune thrombocytopenic purpura or localized lymphoma having normal bone marrow were examined. Two candidate gene approaches, pyrosequencing for NUDT15 and TaqMan assay for thiopurine methyltransferase (TPMT) genotyping (rs1142345 A > G), were performed. We showed a risk allele frequency of NUDT15 of 11.6% in children with ALL and 15.5% in adults. By contrast, the risk allele frequency of TPMT was only 1.6% in children with ALL and 0.5% in adults. The high frequency of risk variant for NUDT15, but not the very low frequency of risk variant for TPMT, was closely associated with the intolerance to mercaptopurine in children with ALL in Taiwan, contrast to that of European descent. In regard to NUDT15 polymorphism, the maximal tolerable daily doses of mercaptopurine in homozygotes, heterozygotes and wild-type groups were 9.4 mgm(-2), 30.7 mgm(-2) and 44.1 mgm(-2), respectively. The outcomes did not differ significantly among the different genotypes.