NUDT15基因多态性与巯基嘌呤所致肝功能异常的相关性分析  

Association between polymorphism of JSUDT15 gene and hepatotoxicity induced by 6-MP in children with acute lymphoblastic leukemia

作　　者：王雪霞 王文杰 Wang Xuexia;Wang Wenjie(Pharmacy Department,Shanxian Central Hospital,Heze,Shandong 274399,China)

机构地区：[1]单县中心医院药剂科,山东274399

出　　处：《中华医学遗传学杂志》2021年第12期1258-1261,共4页Chinese Journal of Medical Genetics

摘　　要：目的探讨儿童急性淋巴细胞白血病(acute lymphoblastic leukemia, ALL)中NUDT15基因单核苷酸多态性(single nucleotide polymorphism, SNP)位点rs116855232多态性与巯基嘌呤(6-mercaptopurine, 6-MP)引起的肝功能损害之间的相关性。方法选取135例入院治疗的ALL患者作为研究对象, 根据治疗过程中肝功能的生化指标分为肝功能损害组及对照组。用Sanger测序的方法确定患者的基因型, SPSS 19.0软件对结果进行统计分析。结果 Sanger结果显示135例患者中99例CC基因型, 32例CT基因型, 4例TT基因型。在治疗初期肝功能受损组与未受损的对照组相比, NUDT15基因rs116855232位点的基因型分布频率差异具有统计学意义(χ^(2)=7.583, P=0.023), T等位基因为风险因子;在维持治疗阶段, 两组基因型分布的差异具有统计学意义(χ^(2)=10591, P=0.005)。结论 NUDT15基因多态性与6-MP药物导致的肝功能受损相关, TT基因型的患者应注意6-MP使用剂量, 避免发生并发症。Objective To investigate the association between single nucleotide polymorphism ofNUDT15 gene(SNP rs116855232)and hepatotoxicity in children with acute lymphocytic leukemia(ALL).Methods A total of 135 children with ALL.in Shandong Province were recruited in this study,and patientswere divided into two groups based on the presence of liver injury.Genotypes of each patient were detectedusing PCR and Sanger sequencing.Clinical data and the average dose of 6-mercaptopurine(6-MP)werecollected and analyzed by SPSS 19.0 software.Results Respectively,99 patients were found with CCgenotype,32 patients with CT genotype and 4 patients with TT genotype.Compared with ALl patientswithout hepatotoxicity,there was a difference in genotypes between the two groups in the initial stage ofchemotherapy for leukemia(χ^(2)=7.583,P=0.023).In maintenance therapy stage there was also adifference between the two groups(χ^(2)=10.591,P=0.005),and T allele was a risk factor forhepatotoxicity.Conclusion The polymorphism of rs116855232 in NUDT15 gene was associated withhepatotoxicity induced by 6-mercaptopurine in children with ALL,and ALL patients with TT genotypeshould take a lower dose of 6-MP to avoided hepatotoxicity.

关 键 词：急性淋巴细胞白血病 NUDT15基因 巯基嘌呤 肝功能受损 

分 类 号：R733.71[医药卫生—肿瘤]