ZHAO Danqi,LI Miao,SHI Zhengyuan,et al.Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors[J].ZHONGGUO YAOFANG,2024,35(21):2646-2651.
ZHAO Danqi,LI Miao,SHI Zhengyuan,et al.Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors[J].ZHONGGUO YAOFANG,2024,35(21):2646-2651. DOI: 10.6039/j.issn.1001-0408.2024.21.12.
Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors
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
2
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 recu
rrence, 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
2
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
2
The
MTRR
rs10380 CC genotype may be a risk factor for electrolyte disorders and tumor metastasis in children with intracranial tumors after MTX chemotherapy.
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