Association analysis of genetic polymorphisms of METTL3 with clinical outcomes in a Chinese pediatric population with primary brain tumors.

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY Gene Pub Date : 2025-03-15 Epub Date: 2025-01-10 DOI:10.1016/j.gene.2025.149232

Shu-Mei Wang, Xiao-Yan Kong, Dan-Qi Zhao, Miao Li

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Abstract

Background: Methyltransferase-like 3 (METTL3) regulates numerous biological processes and diverse cancers.

Objective: To explore the frequency distribution of METTL3 rs1061026, rs1139130, and rs1263801 polymorphisms, and their potential impacts on clinical outcomes and chemotherapy-induced toxicities in a cohort of Chinese pediatric patients diagnosed with primary brain tumors (PBTs).

Methods: Genotyping for three investigated SNPs was performed in 107 pediatric patients with PBTs using the Sequenom MassARRAY iPLEX platform. Serum METTL3 levels were determined by Enzyme-Linked Immunosorbent Assay. Serum methotrexate (MTX) concentrations were quantified utilizing fluorescence polarization immunoassay.

Results: The three investigated SNPs were not significantly associated with the risks of relapse and metastasis after adjusting all confounders. Compared to individuals with the rs1139130 GG genotype, GA genotype carriers exhibited a significantly higher risk of oral mucositis (adjusted OR: 7.504; 95 % CI, 1.931-29.436; P = 0.004). The rs1139130 GA (adjusted OR: 5.091; 95 % CI, 1.351-19.176; P = 0.016) and AA (adjusted OR: 9.588; 95 % CI, 1.769-51.949; P = 0.009) genotype carriers exhibited a significantly lower risk of fever than GG genotype carriers. The median dose-normalized MTX concentrations at 42 h were lower with borderline significance in children with rs1061026 GT and GG genotypes (0.004 μmol/L per g/m²) than the TT genotype carriers (0.006 μmol/L per g/m², P = 0.048). Patients with the rs1139130 GA genotype had significantly higher median serum METTL3 protein levels (59.91 ng/mL) than GG genotype carriers (44.57 ng/mL, P = 0.015).

Conclusion: This study demonstrated the association of the rs1139130 polymorphism with the development of oral mucositis and fever and the rs1061026 polymorphism with MTX exposure.

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METTL3基因多态性与中国儿童原发性脑肿瘤患者临床预后的相关性分析

背景：甲基转移酶样3 （METTL3）调节许多生物过程和多种癌症。目的：探讨METTL3 rs1061026、rs1139130和rs1263801基因多态性的频率分布及其对中国原发性脑肿瘤（PBTs）患儿临床结局和化疗毒性的潜在影响。方法：使用Sequenom MassARRAY iPLEX平台对107例小儿pbt患者的3个snp进行基因分型。采用酶联免疫吸附法测定血清METTL3水平。采用荧光偏振免疫分析法定量测定血清甲氨蝶呤（MTX）浓度。结果：调整所有混杂因素后，3个被调查的snp与复发和转移风险无显著相关。与rs1139130 GG基因型携带者相比，GA基因型携带者患口腔黏膜炎的风险显著增加(校正OR: 7.504；95 % ci, 1.931-29.436； = 0.004页)。rs1139130 GA(调整OR: 5.091；95 % ci, 1.351-19.176；P = 0.016)和AA(调整OR: 9.588；95 % ci, 1.769-51.949；P = 0.009)基因型携带者发热风险明显低于GG基因型携带者。rs1061026 GT和GG基因型患儿42 h时MTX的中位剂量标准化浓度（0.004 μmol/L / g/m2）低于TT基因型携带者（0.006 μmol/L / g/m2, P = 0.048），具有临界意义。rs1139130 GA基因型患者血清METTL3蛋白水平中位数（59.91 ng/mL）显著高于GG基因型携带者（44.57 ng/mL, P = 0.015）。结论：rs1139130基因多态性与口腔黏膜炎和发热的发生有关，rs1061026基因多态性与MTX暴露有关。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.