Association of m1A modification gene polymorphisms with glioma risk in Chinese children

Fan Liao, Rui-Xi Hua, Xingyu Jia, Yuxiang Liao, Li Yuan, Jichen Ruan, Tianfeng Li, Zhenjian Zhuo, Jing He
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Abstract

Glioma is a highly heterogeneous malignancy with a high mortality rate and poor prognosis. m1A methylation modifications are associated with gliomagenesis. However, whether single nucleotide polymorphisms (SNPs) of m1A modification genes are associated with glioma risk is unclear. We successfully genotyped 20 SNPs of m1A-modified genes TRMT10C, TRMT61B, TRMT6, TRM61, ALKBH1, YTHDC1, YTHDF1, and YTHDF2 in 314 pediatric glioma patients and 380 cancer-free controls using TaqMan probes. Associations of polymorphisms with glioma risk were assessed by the odds ratios and 95% confidence intervals generated by logistic regression models. Stratified analysis was performed by age, gender, tumor subtype, and clinical stage. The results showed that TRMT10C rs2303476, TRMT10C rs4257518, TRM61 rs2296484, and YTHDF2 rs3738067 polymorphisms were significantly associated with an increased risk of glioma, TRMT61B rs4563180, YTHDC1 rs2293595, and YTHDC1 rs3813832 polymorphisms were significantly associated with a reduced risk of glioma. In addition, analysis of the expression quantitative trait loci-showed that the TRM61 rs2296484 T allele significantly increased TRM61 messenger RNA (mRNA) expression, the YTHDF2 rs3738067 G allele significantly increased YTHDF2 mRNA expression, and the TRMT61B rs4563180 C allele significantly decreased TRMT61B mRNA expression. Overall, we identified several promising candidates for m1A modification gene polymorphisms as biomarkers of glioma risk.

Abstract Image

m1A修饰基因多态性与中国儿童脑胶质瘤风险的关系
胶质瘤是一种高度异质性的恶性肿瘤,死亡率高,预后差。m1A甲基化修饰与胶质母细胞增多症有关。然而,m1A修饰基因的单核苷酸多态性(SNPs)是否与神经胶质瘤风险相关尚不清楚。我们使用TaqMan探针在314名儿童神经胶质瘤患者和380名无癌对照中成功地对20个m1A修饰基因TRMT10C、TRMT61B、TRMT6、TRM61、ALKBH1、YTHDC1、YTHDF1和YTHDF2的SNPs进行了基因分型。多态性与神经胶质瘤风险的相关性通过逻辑回归模型产生的比值比和95%置信区间进行评估。按年龄、性别、肿瘤亚型和临床分期进行分层分析。结果显示,TRMT10C rs2303476、TRMT10Cs 4257518、TRM61 rs2296484和YTHDF2 rs3738067多态性与胶质瘤风险增加显著相关,TRMT61B rs4563180、YTHDC1 rs2293595和YTHDC1 rss3813832多态性与神经胶质瘤风险降低显著相关。此外,对表达数量性状基因座的分析显示,TRM61 rs2296484 T等位基因显著增加TRM61信使RNA(mRNA)的表达,YTHDF2 rs3738067 G等位基因明显增加YTHDF2 mRNA的表达,TRMT61B rs4563180 C等位基因显着降低TRMT61BmRNA的表达。总体而言,我们确定了几种有希望的m1A修饰基因多态性候选物作为神经胶质瘤风险的生物标志物。
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