Kim Hyoung-Tae, Choi Rihwa, Won Hong-Hee, Choe Yon Ho, Kang Ben, Lee Kiwuk, Koo Hong Hoe, Yoo Keon Hee, Kim Young-Ho, Lee Soo-Youn
Departments of aLaboratory Medicine and Genetics bPediatrics cInternal Medicine dClinical Pharmacology and Therapeutics eSamsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Pharmacogenet Genomics. 2017 May;27(5):197-200. doi: 10.1097/FPC.0000000000000274.
Thiopurines have a narrow therapeutic range because of frequent toxicity (i.e. marrow suppression), which is only partly explained by TPMT genetic polymorphisms, especially within Asian populations. Recent studies have identified NUDT15 variation as another important factor affecting thiopurine metabolism. In this study, a total of four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal) were genotyped in 920 Korean individuals using direct sequencing of NUDT15 for the first time in a Korean population. The allele frequencies were 86.7% for NUDT15*1, and 4.4, 6.9, 0.4, 1.1, and 0.50% for *2, *3, *4, *5, and 6, respectively. The NUDT15 phenotypes based on diplotypes included normal activity (n=692), intermediate activity (n=209), and low activity (n=19), occurring in 75.2, 22.7, and 2.1% of the population, respectively. This study was the first to report NUDT15 variants other than NUDT153 in the Korean population and more individuals who were categorized as having intermediate or low NUDT15 activity in our study than in previously reported studies in the Korean population (24.8 vs. 19.4%, P<0.05). This study is useful for future clinical studies on thiopurine pharmacogenetics and dosage adjustment in the Korean population.
由于硫嘌呤类药物常有毒性（如骨髓抑制），其治疗窗较窄，而TPMT基因多态性只能部分解释这种毒性，在亚洲人群中尤其如此。最近的研究已确定NUDT15变异是影响硫嘌呤代谢的另一个重要因素。在本研究中，首次在韩国人群中对920名韩国个体使用NUDT15直接测序法对总共4种NUDT15编码变体（p.Arg139Cys、p.Arg139His、p.Val18Ile和p.Val18_Val19insGlyVal）进行基因分型。NUDT15*1的等位基因频率为86.7%，*2、*3、4、5和6的等位基因频率分别为4.4%、6.9%、0.4%、1.1%和0.50%。基于双倍型的NUDT15表型包括正常活性（n = 692）、中等活性（n = 209）和低活性（n = 19），分别在人群中的发生率为75.2%、22.7%和2.1%。本研究首次在韩国人群中报告了除NUDT153之外的NUDT15变体，并且与之前韩国人群的研究相比，本研究中被归类为NUDT15活性中等或低的个体更多（24.8%对19.4%，P<0.05）。本研究对韩国人群未来关于硫嘌呤药物遗传学和剂量调整的临床研究具有参考价值。
