Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors
- VernacularTitle:MTRR基因多态性与颅内肿瘤患儿甲氨蝶呤血药浓度及不良反应的相关性研究
- Author:
Danqi ZHAO
1
,
2
;
Miao LI
3
;
Zhengyuan SHI
1
,
4
;
Xiqiao XU
1
,
4
;
Shumei WANG
1
Author Information
1. Dept. of Pharmacy，Beijing Shijitan Hospital，Capital Medical University，Beijing 100038，China
2. Dept. of Clinical Pharmacy，School of Pharmaceutical Sciences，Capital Medical University，Beijing 100069，China
3. Dept. of Pediatrics，Beijing Shijitan Hospital，Capital Medical University，Beijing 100038，China
4. Beijing Key Laboratory of Bio- characteristic Profiling for Evaluation of Rational Drug Use，Beijing 100038，China
- Publication Type:Journal Article
- Keywords:
intracranial tumors;
methotrexate;
methionine synthase reductase;
genetic polymorphism;
adverse reaction;
prognosis
- From:
China Pharmacy
2024;35(21):2646-2651
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the impact of the methionine synthase reductase （MTRR） rs10380 C＞T gene polymorphism on methotrexate （MTX） plasma concentration， adverse drug reaction， and prognosis in children with intracranial tumors. METHODS Peripheral blood was collected from children with intracranial tumors， and genomic DNA was extracted. The MTRR rs10380 C＞T genotype was analyzed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. The association of the MTRR rs10380 C＞T gene polymorphism with the ratio of MTX plasma concentration to dose （C/D ratio）， adverse drug reaction， tumor recurrence， and metastasis was analyzed. Bioinformatics analysis was used to explore the association of the rs10380 genotype and MTRR gene expression and its possible mechanisms. RESULTS A total of 75 children were included in the study. The distribution frequencies of the wild-type CC genotype and C allele of rs10380 were 62.67% and 81.33%， respectively， while the distribution frequencies of the variant CT genotype and T allele were 37.33% and 18.67%， respectively， which were in accordance with Hardy-Weinberg equilibrium（P＞0.05）. The incidence of electrolyte disorders （51.06%） and tumor metastasis rate （57.45%） in children with the CC genotype were significantly higher than those with the CT genotype （P＜0.05）. No significant differences were observed in the 24-hour and 42-hour C/D ratios and recurrence rates between the two genotypes of children （P＞0.05）. Bioinformatics analysis showed that MTRR protein mainly works in conjunction with 10 proteins， including MMAA， and was involved in various biological processes such as sulfur amino acid biosynthesis. CONCLUSIONS The MTRR rs10380 CC genotype may be a risk factor for electrolyte disorders and tumor metastasis in children with intracranial tumors after MTX chemotherapy.
