Effects of MTHFR and GGH gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate therapy in children with acute lymphoblastic leukemia.
10.7499/j.issn.1008-8830.2411059
- Author:
Lin-Xiao TENG
1
;
Qi AN
1
;
Lei WANG
1
;
Nan WANG
1
;
Qing-Ling KONG
1
;
Rui HAN
1
;
Yuan WANG
1
;
Lu LIU
1
;
Yan WANG
1
;
Shu-Mei XU
1
;
Kun-Peng SHI
1
;
Fang-Shan QIU
1
;
Xi-Xi DU
1
;
Jin-Rui SHI
1
Author Information
1. Department of Hematology and Oncology, Xuzhou Children's Hospital, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.
- Publication Type:Journal Article
- Keywords:
Acute lymphoblastic leukemia;
Child;
Methotrexate;
Methylenetetrahydrofolate reductase;
Pharmacogenomics;
Toxicity
- MeSH:
Humans;
Methotrexate/toxicity*;
Methylenetetrahydrofolate Reductase (NADPH2)/genetics*;
Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood*;
Male;
Female;
Child;
Child, Preschool;
gamma-Glutamyl Hydrolase/genetics*;
Antimetabolites, Antineoplastic/adverse effects*;
Infant;
Polymorphism, Genetic;
Adolescent;
Genotype;
Polymorphism, Single Nucleotide
- From:
Chinese Journal of Contemporary Pediatrics
2025;27(7):802-807
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL).
METHODS:Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed.
RESULTS:In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05).
CONCLUSIONS:Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
