Genetic and epigenetic MTHFR gene variants in the mothers of attention-deficit/hyperactivity disorder affected children as possible risk factors for neurodevelopmental disorders.

Aim: To assess promoter methylation levels, gene expression levels and 677C>T/1298A>C genotype and allele frequencies of the MTHFR gene in 45 mothers of attention-deficit/hyperactivity disorder affected child/children (ADHDM) and compare it with age matched healthy control mothers (HCM). Materials & methods: High resolution melting analysis, quantitative real time PCR and PCR-RFLP were performed to assess methylation, gene expression and genotyping, respectively. Significance between ADHDM and HCM was assessed by linear (methylation and gene expression) and logistic regression (genotypes). Results: MTHFR gene expression levels were significantly higher in the ADHDM compared with the HCM group (adj-p < 7.7E-04). No differences in MTHFR promoter methylation level and 677C>T/1298A>C genotype frequencies were detected between ADHDM and HCM. Conclusion: We observed increased MTHFR expression levels not resulting from promoter methylation changes in ADHDM respect to HMC, potentially contributing to the ADHD condition in their children and deserving further investigation.