The correlation between YTHDF1 gene polymorphism and cognitive dysfunction after radiotherapy for glioma

Gliomas are the most common primary malignant tumors of the central nervous system. Mounting evidence highlights the crucial role of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) in glioma treatment response. This study aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of YTHDF1 and cognitive dysfunction (CD) following radiotherapy for glioma.

A total of 323 glioma patients were enrolled pre-radiotherapy and followed up for 3 months post-radiotherapy. They were categorized into glioma patients with CD (group, n = 202) and glioma patients without CD (non-CD group, n = 121). YTHDF1 mRNA expression was measured in peripheral blood samples collected before radiotherapy using RT-qPCR. Four YTHDF1 SNPs (rs6011668, rs6090311, rs68041888 and rs6122103) were genotyped via PCR-RFLP. Multivariate logistic regression was further performed to verify the association between YTHDF1 polymorphisms and post-radiotherapy CD.

YTHDF1 mRNA expression was significantly higher in the CD group than in the non-CD group. Among the four analyzed SNPs, only rs6090311 exhibited significant differences in both genotype and allele frequencies between the two groups, while rs6011668, rs68041888 and rs6122103 showed no significant variations. After controlling for potential confounders, including WHO grade, tumor volume, BDNF levels, and radiotherapy dose, carriers of the G allele (A/G + G/G genotypes) at rs6090311 demonstrated a significantly lower risk of developing post-radiotherapy CD (OR = 0.319, 95% CI: 0.111-0.916).

YTHDF1 overexpression is associated with post-radiotherapy CD in glioma patients, and the rs6090311 G allele may act as a protective genetic marker for this complication.