Lin Huiran, Liao Fan, Liu Jiabin, Yang Zhonghua, Zhang Jiao, Cheng Jiwen, Zhou Haixia, Li Suhong, Li Li, Li Yong, Zhuo Zhenjian, He Jing
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, Guangdong, China.
Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, China.
Pediatr Res. 2025 Jan;97(1):153-159. doi: 10.1038/s41390-024-03318-w. Epub 2024 Jun 13.
Neuroblastoma (NB) is a common extracranial solid malignancy in children. The N7-methylguanosine (mG) modification gene METTL1/WDR4 polymorphisms may serve as promising molecular markers for identifying populations susceptible to NB.
TaqMan probes was usded to genotype METTL1/WDR4 single nucleotide polymorphisms (SNPs) in 898 NB patients and 1734 healthy controls. A logistic regression model was utilized to calculate the odds ratio (OR) and 95% confidence interval (CI), evaluating the association between genotype polymorphisms and NB susceptibility. The analysis was also stratified by age, sex, tumor origin site, and clinical stage.
Individual polymorphism of the METTL1/WDR4 gene investigated in this study did not show significant associations with NB susceptibility. However, combined genotype analysis revealed that carrying all 5 WDR4 protective genotypes was associated with a significantly lower NB risk compared to having 0-4 protective genotypes (AOR = 0.82, 95% CI = 0.69-0.96, P = 0.014). Further stratified analyses revealed that carrying 1-3 METTL1 risk genotypes, the WDR4 rs2156316 CG/GG genotype, the WDR4 rs2248490 CG/GG genotype, and having all five WDR4 protective genotypes were all significantly correlated with NB susceptibility in distinct subpopulations.
In conclusion, our findings suggest significant associations between mG modification gene METTL1/WDR4 SNPs and NB susceptibility in specific populations.
Genetic variation in mG modification gene is associated with susceptibility to NB. Single nucleotide polymorphisms in METTL1/WDR4 are associated with susceptibility to NB. Single nucleotide polymorphisms of METTL1/WDR4 can be used as a biomarker for screening NB susceptible populations.
神经母细胞瘤（NB）是儿童常见的颅外实体恶性肿瘤。N7-甲基鸟苷（mG）修饰基因METTL1/WDR4多态性可能是识别NB易感人群的有前景的分子标志物。
采用TaqMan探针技术对898例NB患者和1734例健康对照者的METTL1/WDR4单核苷酸多态性（SNP）进行基因分型。利用逻辑回归模型计算比值比（OR）和95%置信区间（CI），评估基因多态性与NB易感性之间的关联。分析还按年龄、性别、肿瘤起源部位和临床分期进行分层。
本研究中所研究的METTL1/WDR4基因的个体多态性与NB易感性无显著关联。然而，联合基因型分析显示，与携带0 - 4种保护基因型相比，携带所有5种WDR4保护基因型与显著降低的NB风险相关（调整后OR = 0.82，95% CI = 0.69 - 0.96，P = 0.014）。进一步的分层分析显示，携带1 - 3种METTL1风险基因型、WDR4 rs2156316 CG/GG基因型、WDR4 rs2248490 CG/GG基因型以及携带所有5种WDR4保护基因型均与不同亚组中的NB易感性显著相关。
总之，我们的研究结果表明mG修饰基因METTL1/WDR4 SNP与特定人群中的NB易感性之间存在显著关联。
mG修饰基因的遗传变异与NB易感性相关。METTL1/WDR4中的单核苷酸多态性与NB易感性相关。METTL1/WDR4的单核苷酸多态性可作为筛选NB易感人群的生物标志物。
