Retrospective cohort study on the relationship between MTHFR and ABCB1 gene polymorphisms and high-dose methotrexate toxicity in children with acute lymphoblastic leukemia
10.13699/j.cnki.1001-6821.2024.13.024
- VernacularTitle:MTHFR及ABCB1基因多态性与急性淋巴细胞白血病患儿大剂量甲氨蝶呤药物不良反应关系
- Author:
Rui XU
1
;
Jing LI
;
Yu HU
;
Li-fu Wu-jü-dan·A MAI
;
Rui ZHANG
;
Wen JIANG
;
Xuan SUN
;
Lin WANG
;
Jun ZHAO
Author Information
1. 新疆医科大学第六附属医院药学部,新疆维吾尔自治区乌鲁木齐 830002
- Keywords:
acute lymphoblastic leukemia;
children;
high dose methotrexate;
methylenetetrahydrofolate reductase;
multidrug resistance 1;
adverse drug reaction
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(13):1963-1967
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the relationship between methylenetetrahydrofolate reductase(MTHFR)C677T,A1298C and multidrug resistance 1(ABCB1)C3435T gene polymorphisms and the adverse reactions of high-dose methotrexate(HD-MTX)in children with acute lymphoblastic leukemia(ALL).Methods Blood samples of ALL children treated with HD-MTX chemotherapy were collected,and the polymorphic polymorphism of MTHFR C677T,A1298C and ABCB1 C3435T genes were detected by sequencing method.The adverse drug reactions after MTX chemotherapy were evaluated according to the common adverse drug reaction grading criteria.The relationship between MTHFR C677T,A1298C and ABCB1 C3435T gene polymorphisms and HD-MTX adverse drug reactions was analyzed.Results The risk of MTHFR A1298C AC+CC type hepatic injury(grade 2)was higher than AA type[odds ratio(OR)2.350,95％confidence interval(CI)=1.038-5.320,P＜0.05],no correlations were found between MTHFR A1298C and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).ABCB1 C3435T CT type hepatic injury(grade 2)was higher than TT type(OR 5.161,95％CI 1.371-19.424,P＜0.05),ABCB1 C3435T CC+CT type hepatic injury(grade 2)was higher than TT type(OR 4.231,95％CI 1.165-15.362,P＜0.05);no correlations were found between ABCB1 C3435T and myelosuppression,mucositis,gastrointestinal reaction and acute renal impair(all P＞0.05).No correlations wre found between MTHFR C677T and HD-MTX adverse drug reactions(all P＞0.05).Conclusion When treating ALL with HD-MTX,adverse drug reactions can be predicted by detecting MTHFR A1298C and ABCB1 C3435T genotypes,so as to implement more scientific individualized medication.
