Wang Shu-Mei, Kong Xiao-Yan, Zhao Dan-Qi, Li Miao
Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.
Department of Pharmacy, Armed Police Beijing Corps Hospital, Beijing, China.
Gene. 2025 Mar 15;941:149232. doi: 10.1016/j.gene.2025.149232. Epub 2025 Jan 10.
Methyltransferase-like 3 (METTL3) regulates numerous biological processes and diverse cancers.
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).
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.
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/m) than the TT genotype carriers (0.006 μmol/L per g/m, 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).
This study demonstrated the association of the rs1139130 polymorphism with the development of oral mucositis and fever and the rs1061026 polymorphism with MTX exposure.
甲基转移酶样3（METTL3）调节众多生物学过程及多种癌症。
探讨甲基转移酶样3（METTL3）基因rs1061026、rs1139130和rs1263801多态性的频率分布，及其对一组诊断为原发性脑肿瘤（PBT）的中国儿科患者临床结局和化疗诱导毒性的潜在影响。
使用Sequenom MassARRAY iPLEX平台对107例患有PBT的儿科患者进行三个研究单核苷酸多态性（SNP）的基因分型。采用酶联免疫吸附测定法测定血清METTL3水平。利用荧光偏振免疫测定法定量血清甲氨蝶呤（MTX）浓度。
在调整所有混杂因素后，三个研究的SNP与复发和转移风险无显著关联。与rs1139130 GG基因型个体相比，GA基因型携带者发生口腔黏膜炎的风险显著更高（校正比值比：7.504；95%置信区间，1.931 - 29.436；P = 0.004）。rs1139130 GA（校正比值比：5.091；95%置信区间，1.351 - 19.176；P = 0.016）和AA（校正比值比：9.588；95%置信区间，1.769 - 51.949；P = 0.009）基因型携带者发热风险显著低于GG基因型携带者。rs1061026 GT和GG基因型儿童在42小时时的中位剂量标准化MTX浓度（每克/米体表面积0.004μmol/L）低于TT基因型携带者（每克/米体表面积0.006μmol/L，P = 0.048），差异具有临界显著性。rs1139130 GA基因型患者的血清METTL3蛋白中位水平（59.91 ng/mL）显著高于GG基因型携带者（44.57 ng/mL，P = 0.015）。
本研究证明rs1139130多态性与口腔黏膜炎和发热的发生相关，rs1061026多态性与MTX暴露相关。
