NUDT 15基因多态性与巯嘌呤类药物耐受性及其所致白细胞减少的研究进展

Research Progress on the Association Between NUDT 15 Polymorphism and Intolerance of Thiopurine and Thiopurine-induced Leukopenia

关键词:  巯嘌呤  NUDT 15  基因多态性  耐受性  白细胞减少  骨髓抑制

Key words:  thiopurine  NUDT 15  polymorphism  tolerance  leukopenia  myelosuppression

摘要:

目的 综述NUDT 15基因多态性与巯嘌呤类药物耐受性及其所致白细胞减少的研究，以期为巯嘌呤类药物在临床中的应用提供参考。方法 检索国内外相关文献，进行整理和综合分析。结果 研究人群主要集中在亚洲，大多为韩国和日本人，在中国儿童急性淋巴细胞白血病患者中仅有2个人群的研究，在中国炎症性肠病患者中有3个相关研究。大多数研究显示在亚洲人群中NUDT 15 c.415 C>T位点突变与巯嘌呤类药物的耐受性及相关白细胞减少有关，此外多个在炎症性肠患者群中的研究发现c.415 C>T纯合突变可能与严重脱发有关。结论 大多数研究显示亚洲人群NUDT 15 c.415 C>T位点突变与巯嘌呤类药物的耐受性及相关白细胞减少有关，该位点的测定可能会优化巯嘌呤类药物在临床中的应用，但其他NUDT 15基因位点突变相关的研究较少，还需要进一步探究。

Abstract:

OBJECTIVE To review researches on the association between NUDT 15 polymorphism and tolerance of thiopurine, thiopurine-induced leukopenia, hoping which can provide some help for its better clinical application. METHODS Searched domestic and foreign related literature, organized and comprehensive analyzed. RESULTS The people studied were mainly Asian, especially Korean and Japanese. However, there was only two studies in child acute lymphoblastic leukemia and 3 studies in inflammatory bowel disease in China. Most studies revealed that NUDT 15 c.415 C>T mutation was strongly associated with intolerance of thiopurines and thiopurine-induced leukopenia especially in Asians. Besides, several studies in inflammatory bowel disease also found that patients with c.415 C>T homozygous mutation were easier to develop severe hair loss. CONCLUSION Most studies have revealed that NUDT 15 c.415 C>T mutation is strongly associated with intolerance of thiopurines and thiopurine-induced leukopenia especially in Asians. Genotyping c.415 C>T genotype might provide help for a better clinical reaction. Whereas, researches on NUDT 15 other variants is few and need to explore further their.