Exploration of Homocysteine Metabolism and Genetics in Autism Spectrum Disorder

Understanding the genetic and metabolic profiles of individuals diagnosed with Autism Spectrum Disorder (ASD) is important for clarifying the biological characteristics of this complex disorder.

Given the limited data available for the Lebanese population, this case-control study aimed to investigate the association between common MTHFR variants and ASD risk and to examine differences in homocysteine metabolism between Lebanese individuals with ASD and neurotypical controls.

From June 2022 to June 2023, 86 individuals with ASD and 86 controls matched for age and sex were recruited. Genotyping of the rs1801133 and rs1801131 variants and biochemical measurements were performed, followed by comparative statistical analyses.

Our results showed no significant association between the rs1801133 or rs1801131 variants and ASD risk (p > 0.05). However, the sample size was not sufficient to rule out small genetic effects. Metabolic analyses revealed significantly higher homocysteine concentrations and lower vitamin B9 levels in the ASD group (p < 0.0001), while vitamin B12, fasting glucose, and lipid profiles did not differ significantly between groups (p > 0.05). Among individuals with ASD, the TT genotype of rs1801133 was associated with elevated homocysteine concentrations (OR = 9.10, p = 0.014), whereas neither MTHFR variant was associated with vitamin B12 or B9 levels in ASD or control participants.

Future research directions could focus on exploring the role of key enzymes associated with hyperhomocysteinemia in individuals with ASD and on replicating these preliminary findings in larger, adequately powered cohorts.