Effects of GGH genetic polymorphisms on serum concentrations and chemotherapy toxicities of methotrexate in children with intracranial tumors
10.13699/j.cnki.1001-6821.2025.02.007
- VernacularTitle: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
- Author:
Dan-qi ZHAO
1
;
Zheng-yuan SHI
;
Xi-qiao XU
;
Shu-mei WANG
Author Information
1. 首都医科大学附属北京世纪坛医院药学部,北京 100038;,首都医科大学药学院临床药学系,北京 100069
- Publication Type:Journal Article
- Keywords:
methotrexate;
intracranial tumor;
γ-glutamyl hydrolase;
genetic polymorphism
- From:
The Chinese Journal of Clinical Pharmacology
2025;41(2):183-187
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of γ-glutamyl hydrolase(GGH)rs11545078 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＞T polymorphisms.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 rs11545078 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 rs11545078 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 0.14 μmol·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 0.11 μmol·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 rs11545078 CT might be a risk factor for gastrointestinal disorders in children with intracranial tumors treated with MTX.
