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, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, 510623 Guangdong, China.
Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang, China.
Biomed Res Int. 2023 Jan 24;2023:3678327. doi: 10.1155/2023/3678327. eCollection 2023.
Glioma stemming from glial cells of the central nervous system (CNS) is one of the leading causes of cancer death in childhood. The genetic predisposition of glioma is not fully understood. METTL1-WDR4 methyltransferase complex is implicated in tumorigenesis by catalyzing N7-methylguanosine (mG) modification of RNA. This study is aimed at determining the association of glioma risk with three polymorphisms (rs2291617, rs10877013, and rs10877012) in and five polymorphisms (rs2156315 rs2156316, rs6586250, rs15736, and rs2248490) in gene in children of Chinese Han. We enrolled 314 cases and 380 controls from three independent hospitals. Genotypes of these polymorphisms were determined using the TaqMan assay. We found the gene rs15736 was significantly associated with reduced glioma risk (GA/AA vs. GG: adjusted odds ratio = 0.63, 95%confidence interval = 0.42 - 0.94, = 0.023) out of the eight studied polymorphisms. Stratified analyses showed that the association of rs15736 with the risk of glioma remained significant in children aged 60 months or older, girls, the subgroups with astrocytic tumors, or grade I + II glioma. We also found the combined effects of five gene polymorphisms on glioma risk. Finally, expression quantitative trait locus (eQTL) analyses elucidated that the rs15736 polymorphism was related to the expression level of and neighboring gene (). Our finding provided evidence of a causal association between gene polymorphisms and glioma susceptibility in Chinese Han children.
中枢神经系统（CNS）胶质细胞来源的神经胶质瘤是儿童癌症死亡的主要原因之一。神经胶质瘤的遗传易感性尚未完全阐明。METTL1-WDR4 甲基转移酶复合物通过催化 RNA 的 N7-甲基鸟苷（mG）修饰而参与肿瘤发生。本研究旨在确定三个多态性（rs2291617、rs10877013 和 rs10877012）和五个多态性（rs2156315、rs2156316、rs6586250、rs15736 和 rs2248490）与中国汉族儿童神经胶质瘤风险的关联。我们从三家独立医院招募了 314 例病例和 380 例对照。使用 TaqMan 测定法确定这些多态性的基因型。我们发现，在研究的 8 个多态性中，基因 rs15736 与降低的神经胶质瘤风险显著相关（GA/AA 与 GG：调整后的优势比=0.63，95%置信区间=0.42-0.94，=0.023）。分层分析表明，rs15736 与神经胶质瘤风险的关联在 60 个月或以上的儿童、女孩、星形细胞瘤亚组或 I + II 级神经胶质瘤亚组中仍然显著。我们还发现了五个基因多态性对神经胶质瘤风险的联合作用。最后，表达数量性状基因座（eQTL）分析表明，rs15736 多态性与基因和邻近基因的表达水平有关（）。我们的研究结果提供了中国汉族儿童中基因多态性与神经胶质瘤易感性之间因果关联的证据。
