颅内肿瘤患儿GGH基因多态性对甲氨蝶呤血清浓度和化疗毒性的影响  

Effects of GGH genetic polymorphisms on serum concentrations and chemotherapy toxicities of methotrexate in children with intracranial tumors

作　　者：赵丹琪 时正媛 续茜桥 王淑梅 ZHAO Dan-qi;SHI Zheng-yuann;XU Xi-qiao;WANG Shu mei(Department of Pharmacy,Bejing Shijitan Hospital,Capital Medical University,Bejing 100038,China;Department of Clinical Pharmacy,College of Pharmacy,Capital Medical University,Beijing 100069,China;Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Rational Drug Use,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院药学部,北京100038 [2]首都医科大学药学院临床药学系,北京100069 [3]临床合理用药生物特征谱学评价北京市重点实验室,北京100038

出　　处：《中国临床药理学杂志》2025年第2期183-187,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81872926);临床合理用药生物特征谱学评价北京市重点实验室基金资助项目(BZ0439);首都医科大学附属北京世纪坛医院院基金资助项目(2023-C01)。

摘　　要：目的考察颅内肿瘤患儿γ-谷氨酰水解酶(GGH)rs11545078 C>T基因多态性对甲氨蝶呤(MTX)血清浓度、化疗毒性和预后的影响。方法收集颅内肿瘤患儿的外周血,提取基因组DNA,用基质辅助激光解吸电离飞行时间质谱技术分析GGH rs11545078 C>T基因型,用荧光偏振免疫法测定血清MTX浓度,记录MTX化疗毒性和颅内肿瘤复发、转移情况,分析GGH rs11545078 C>T基因多态性与剂量校正的MTX浓度[浓度与剂量比值(C/D比值)]、化疗毒性、肿瘤复发和转移的相关性。结果研究共纳入患儿75例,rs11545078 CC和CT基因型的分布频率分别为82.67%和17.33%,C和T等位基因的分布频率分别为91.33%和8.67%,与血液肿瘤患儿和北京健康人群中的分布均无显著性差异。CC基因型患儿的24和42 h中位C/D比值(25.19和0.14μmol·L^(-1)perg·m^(-2))高于CT基因型患儿(22.01和0.11μmol·L^(-1)perg·m^(-2)),转移率(46.77%)高于CT基因型患儿(38.46%),复发率(17.74%)低于CT基因型患儿(30.77%),但在统计学上差异均无统计学意义(均P>0.05)。CT基因型患儿的胃肠道不良事件发生率(76.92%)显著高于CC基因型患儿(45.16%,P<0.05),其余不良事件的发生率在统计学上差异均无统计学意义(均P>0.05)。结论GGH rs11545078 CT基因型可能是颅内肿瘤患儿发生胃肠道不良事件的危险因素。Objective To investigate the effects of-glutamyl hydrolase(GGH)rs115450788 C>T polymorphisms on serum concentrations,chemotherapy toxicities of methotrexate(MTX),and prognosis in children with intracranial tumors.Methods Peripheral blood samples were obtained from children with intracranial tumors to extract genome DNA.Matrix-assisted laser desorption/ionization-time of flight mass spectrometry was used to detect the genotypes of GGH rs11545078 C>Tpolymorphisms.Fluorescence polarization immunoassay was employed to determine the serum concentrations of MTX.The incidences of toxicities,relapse,and metastasis were recorded after chemotherapy with MTX.The associations of GGH rsl1545078 C>T polymorphisms with concentration-to-dose ratios(C/D ratios),chemotherapy toxicities of MTX,relapse,and metastasis of tumors were analyzed.Results A total of 75 children were included in the present study.The frequencies of rsl1545078 CC and CT genotypes were 82.67%and 17.33%,respectively.The frequencies of C and T alleles were 91.33%and 8.67%,respectively.There were no statistically significant differences for these frequencies among the children with intracranial tumors,the children with acute lymphoblastic leukemia,and the health population in Beijing.Children with the CC genotype had higher median C/D ratios of MTX in 24 and 42 h(25.19 and 0.14μmol·L^(-1)per g·m^(-2),respectively),higher metastasis rates(46.77%),and lower relapse rates(17.74%)than those in CT genotype carriers(22.01 and 0.11μmol·L^(-1)per g·m^(-2),38.46%,and 30.77%,respectively),and the differences were no statistically significant(all P>0.05).The incidences of gastrointestinal disorders(76.92%)in children with the CT genotype were significantly higher than those in CC genotype carriers(45.16%,P<0.05).There were no statistically significant differences in the incidences of other adverse events between patients with the CC genotype and patients with the CT genotype(all P>0.05).Conclusion GGH rsl1545078 CT might be a risk factor for gastrointestinal disorder

关 键 词：甲氨蝶呤 颅内肿瘤 γ-谷氨酰水解酶 基因多态性 

分 类 号：R979.1[医药卫生—药品]