Genetic variants in m6A modification core genes are associated with glioma risk in Chinese children

Abstract

Glioma is a highly heritable disease with a strong genetic component. The N6-methyladenosine (m6A) modification core genes play important roles in the context of cancer. However, the effects of polymorphisms in the m6A modification core genes on the risk of pediatric glioma remain undefined. Here, we intended to demonstrate the relationship between 24 functional single-nucleotide polymorphisms (SNPs) in eight m6A modification core genes and glioma risk. Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma while accounting for the subtypes of glioma. A total of 171 glioma cases and 228 controls from South China were genotyped using a TaqMan assay. The WTAP rs7766006, YTHDF2 rs3738067, and FTO rs9939609 variants conferred a statistically significant increased risk of glioma, respectively. YTHDC1 rs2293595, YTHDC1 rs3813832, and FTO rs8047395 were associated with a significant inverse association with risk of glioma, respectively. The significant associations were more predominant in stratification analyses of certain subgroups. Functional annotations revealed that WTAP rs7766006 and YTHDF2 rs3738067 could be potential functional variants by increasing expression of WTAP and YTHDF2 mRNA, respectively. Overall, these findings implicate variants in the m6A modification core genes as playing a role in pediatric glioma etiology.