NUDT15基因多态性与巯嘌呤类药物所致白细胞减少的研究进展.docxVIP

NUDT15基因多态性与毓嚓吟类药物所致 白细胞减少的研究进展 费祥束庆葛卫红方芸 南京大学医学院附属鼓楼医院药学部中国药科大学 基础医学与临床药学学院 摘要： 硫哇卩票吟(azathioprine, AZA)和 6-疏基瞟吟(6-niercaptopurine, 6-MP)被 广泛用于炎症性肠病、急性淋巴细胞白血病的治疗，但以白细胞减少为主的不良 反应一直是困扰临床安全用药的难题。研究发现个体间的基因差异与该不良反应 密切相关，美国食品药品监督管理局早在2005年就推荐服药前进行硫卩票岭类药 物代谢相关的铳基瞟吟甲基转移酶(TPMT)的基因型检测以评估口细胞减少不 良反应的发生，但该位点不能很好地预防亚洲人群中该不良反应的频发。新近研 究提示NUDT15基因位点与亚洲人群的白细胞减少更密切，木文将综述NUDT15 位点与亚洲人群服用AZA/6-MP后岀现的白细胞减少之间的相关性研究。 关键词： 硫醴瞟吟;NUDT15;白细胞减少;基因多态性;亚洲人群; 作者简介：费祥，男，硕士研究生在读，研究方向：临床药学；电 话E-mail:fx29_cpu@163. com 作者简介：方芸，女，主任药师，硕士生导师，研究方向：临床合理用药和中药 药理;电话:025E-mail:njglfy@163. com 收稿日期:2017-03-05 基金：江苏省戻学创新团队(领军人才)：以甲氨蝶吟为例，整合多维药学服务 技术搭建精准用药应用研究平台项目的资助 Advances in genetic polymorphism of NUDT15 and leucopenia caused by thiopurines FEI Xiang SHU Qing GE Wei—hong FANG Yun Department of Pharmacy, Affiliated Drum Tower Hospital of Nanjing University Medical School; Abstract： Azathioprine (AZA) and 6-mercaptopurine (6-MP) are widely used in inflommatory bowel disease and acute lymphoblastic leukemia. However, lcucopcnia based adverse reactions have been problems in cl inical application. America Food and Drug Administration recommended thiopurine S-meth)4transferase (TPMT) genotype test to avoid thiopurine related leucopenia in 2005 since previous study found that the genetic polymorphism between individuals were closely related to this adverse event. However, this genetic locus cemnot predict very well with leucopenia in Asia populations clue to the low mutation frequency. Recently, more and more studies suggest that NUDT15 can be a potential locus to predict thiopurine related leucopenia better than TPMT in Asia populations. Thi s review aims to con elude the re la tio nship bet wee n NUDT15 and leucopenia in Asian populations. Keyword： dznthioprine; NUDT15; leucopenia; genetic polymorphism; Asia population; Received： 2017-03-05 硫卩坐卩票吟(azathiopri ne, AZA)和6-硫基卩票吟(6-祇2卯3卩11门阴，6-MP)是 卩票岭类免疫抑制剂，主要通过干扰卩票岭代谢，影响卩票岭核廿酸的合成，进而抑 制细胞DNA、RNA及蛋口质的合成。目前指南推荐其作为炎症性肠病 (inflammatory bowel dise