Associations of <italic style="font-style: italic">MTRR </italic>gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors

ZHAO Danqi; LI Miao; SHI Zhengyuan; XU Xiqiao; WANG Shumei

doi:10.6039/j.issn.1001-0408.2024.21.12

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Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors

更新时间：2025-09-25

- Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors
- ZHONGGUO YAOFANG Vol. 35, Issue 21, Pages: 2646-2651(2024)
- 作者机构：
  
  1.首都医科大学附属北京世纪坛医院药学部，北京　100038
  2.首都医科大学药学院临床药学系，北京　100069
  3.首都医科大学附属北京世纪坛医院儿科，北京　100038
  4.临床合理用药生物特征谱学评价北京市重点实验室，北京　100038
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2024.21.12
  CLC： R969
- Received：08 July 2024，
  
  Revised：2024-09-06，
  
  Accepted：10 October 2024，
  
  Published：15 November 2024
- 稿件说明：
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赵丹琪,李苗,时正媛,等.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[J].中国药房,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.
赵丹琪,李苗,时正媛,等.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[J].中国药房,2024,35(21):2646-2651. DOI： 10.6039/j.issn.1001-0408.2024.21.12.

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.

摘要

目的

考察颅内肿瘤患儿甲硫氨酸合成酶还原酶（

MTRR

）rs10380 C＞T基因多态性对甲氨蝶呤（MTX）血药浓度、不良反应和预后的影响。

方法

收集颅内肿瘤患儿的外周血，提取基因组DNA，用基质辅助激光解吸电离-飞行时间质谱法分析

MTRR

rs10380 C＞T基因型，分析

MTRR

rs10380 C＞T基因多态性与MTX血药浓度和剂量之间的比值（C/D比值）、不良反应、肿瘤复发和转移的相关性。基于生物信息学分析探索rs10380基因型与

MTRR

基因表达的关系及其可能机制。

结果

研究共纳入患儿75例，rs10380 野生CC基因型和C等位基因的分布频率分别为62.67%和81.33%，变异CT基因型和T等位基因的分布频率分别为37.33%和18.67%，符合Hardy-Weinberg平衡（

＞0.05）。CC基因型患儿的电解质紊乱发生率（51.06%）和肿瘤转移率（57.45%）显著高于CT基因型患儿（

＜0.05）。两种基因型患儿的24 h和42 h C/D比值、复发率差异无统计学意义（

＞0.05）。生信分析结果显示，MTRR蛋白主要与MMAA等10种蛋白协同发挥作用，并参与了含硫氨基酸生物合成等多种生物过程。

结论

MTRR

rs10380 CC基因型可能是颅内肿瘤患儿MTX化疗后电解质紊乱和肿瘤转移的危险因素。

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 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

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 （

＞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 （

＜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 （

＞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.

关键词

Keywords

references

NERADIL J ， PAVLASOVA G ， VESELSKA R . New mechanisms for an old drug； DHFR- and non-DHFR-mediated effects of methotrexate in cancer cells [J ] . Klin Onkol ， 2012 ， 25 （ Suppl. 2 ）： S87 - S92 .

PANETTA J C ， ROBERTS J K ， HUANG J ， et al . Pharmacokinetic basis for dosing high-dose methotrexate in infants and young children with malignant brain tumors [J ] . Br J Clin Pharmacol ， 2020 ， 86 （ 2 ）： 362 - 371 .

宋再伟，刘爽，赵荣生，等 . 《中国大剂量甲氨蝶呤循证用药指南》解读 [J ] . 中国药房， 2022 ， 33 （ 16 ）： 2032 - 2039 .

SONG Z W ， LIU S ， ZHAO R S ， et al . Interpretation for Evidence-based Practice Guideline of Medication Therapy of High-dose Methotrexate in China [J ] . China Pharm ， 2022 ， 33 （ 16 ）： 2032 - 2039 .

LECLERC D ， WILSON A ， DUMAS R ， et al . Cloning and mapping of a cDNA for methionine synthase reductase，a flavoprotein defective in patients with homocystinuria [J ] . Proc Natl Acad Sci USA ， 1998 ， 95 （ 6 ）： 3059 - 3064 .

王连珂，张程达，田丹丹，等 . MTRR基因多态性对口服叶酸治疗HHcy效果的影响 [J ] . 现代预防医学， 2016 ， 43 （ 6 ）： 1134 - 1137 .

WANG L K ， ZHANG C D ， TIAN D D ， et al . The influence of MTRR gene polymorphisms on the efficacy of oral folic acid in the treatment of hyperhomocysteinemia [J ] . Mod Prev Med ， 2016 ， 43 （ 6 ）： 1134 - 1137 .

OHNAMI S ， SATO Y ， YOSHIMURA K ， et al . His595Tyr polymorphism in the methionine synthase reductase （MTRR） gene is associated with pancreatic cancer risk [J ] . Gastroenterology ， 2008 ， 135 （ 2 ）： 477 - 488 .

LOUIS D N ， PERRY A ， WESSELING P ， et al . The 2021 WHO classification of tumors of the central nervous system：a summary [J ] . Neuro Oncol ， 2021 ， 23 （ 8 ）： 1231 - 1251 .

LI M ， KONG X Y ， WANG S M . Effects of splicing-regulatory polymorphisms in ABCC2，ABCG2，and ABCB1 on methotrexate exposure in Chinese children with acute lymphoblastic leukemia [J ] . Cancer Chemother Pharmacol ， 2023 ， 91 （ 1 ）： 77 - 87 .

U.S. Department of Health and Human Services . Common terminology criteria for adverse events （CTCAE） version 5.0 [EB/OL ] .（ 2017-11-27 ）[ 2024-09-10 ] . https：//ctep. cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf .

QUAN C ， PING J ， LU H ， et al . 3DSNP 2.0：update and expansion of the noncoding genomic variant annotation database [J ] . Nucleic Acids Res ， 2022 ， 50 （ D1 ）： D950 - D955 .

WARD L D ， KELLIS M . HaploReg：a resource for explo- ring chromatin states，conservation，and regulatory moti- falterations within sets of genetically linked variants [J ] . Nucleic Acids Res ， 2012 ， 40 （ Database issue ）： D930 - D934 .

FONG C S ， SHYU H Y ， SHIEH J C ， et al . Association of MTHFR，MTR，and MTRR polymorphisms with Parkinson’s disease among ethnic Chinese in Taiwan [J ] . Clin Chim Acta ， 2011 ， 412 （ 3/4 ）： 332 - 338 .

马利敏，阮林海，刘洪超，等 . MTRR基因A66G多态性与儿童急性淋巴细胞白血病关系的Meta分析 [J ] . 肿瘤防治研究， 2015 ， 42 （ 8 ）： 824 - 828 .

MA L M ， RUAN L H ， LIU H C ， et al . MTRR gene A66G polymorphism and pediatric acute lymphoblastic leukemia：a meta-analysis [J ] . Cancer Res Prev Treat ， 2015 ， 42 （ 8 ）： 824 - 828 .

LI M ， KONG X Y ， WANG S M . Analysis of the frequency distribution of five single-nucleotide polymorphisms of the MTRR gene in a Chinese pediatric population with acute lymphoblastic leukemia [J ] . Pharmacotherapy ， 2022 ， 42 （ 6 ）： 442 - 452 .

LI M ， WANG S M ， WU W S ， et al . Frequency distribution of five SNPs in human GGH gene and their effects on clinical outcomes of Chinese pediatric patients with acute lymphoblastic leukemia [J ] . Pharmazie ， 2020 ， 75 （ 4 ）： 142 - 146 .

PITAKKITNUKUN P ， PONGPITAKMETHA T ， SUTTICHET T B ， et al . Genetic polymorphisms and clinical parameters associated with renal toxicity in Thai hematologic malignancy patients receiving high dose methotrexate [J ] . Sci Rep ， 2024 ， 14 （ 1 ）： 9695 .

何霞，姚平立，吴宇，等 . MTRR和SLCO1B1基因多态性与ALL患儿MTX血药浓度及HD-MTX致不良反应的相关性研究 [J ] . 中国药房， 2019 ， 30 （ 24 ）： 3428 - 3433 .

HE X ， YAO P L ， WU Y ， et al . Study on relationships of gene polymorphism of MTRR and SLCO1B1 with blood concentration of MTX and HD-MTX-induced ADR in ALL children [J ] . China Pharm ， 2019 ， 30 （ 24 ）： 3428 - 3433 .

ASNAFI A A ， BEHZAD M M ， GHANAVAT M ， et al . Single nucleotide polymorphisms in osteosarcoma：pathogenic effect and prognostic significance [J ] . Exp Mol Pathol ， 2019 ， 106 ： 63 - 77 .

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⁰

Associations of MTRR gene polymorphism and methotrexate plasma concentration and adverse drug reaction in children with intracranial tumors

DOI：10.6039/j.issn.1001-0408.2024.21.12

摘要

Abstract

关键词

Keywords

references