Catalase Gene Variants and Oxidative Stress in Autism Spectrum Disorder: A Northern Lebanon Cohort and Aripiprazole In Vitro Toxicity.

Researchers studied whether a specific gene variant affects autism risk in 94 Lebanese participants and found no connection. They also tested how the autism medication aripiprazole affects cells in the lab. The medication caused more harm to cells missing certain protective genes, suggesting that a person's genetics might influence how they respond to this treatment.

This study investigated whether a specific genetic variant in the catalase gene (rs7943316) is associated with autism spectrum disorder in a Lebanese population of 94 participants (39 with ASD, 55 controls). No significant association was found between this genetic variant and ASD risk. The researchers also examined how aripiprazole, a commonly prescribed autism medication, affects yeast cells with different genetic modifications. They found that aripiprazole causes dose-dependent toxicity, with cells lacking certain genes related to oxidative stress and metabolism being more sensitive to the drug's harmful effects.

The findings suggest that genetic factors may influence how individuals respond to aripiprazole treatment.

Results suggest genetic screening might help predict aripiprazole sensitivity, though more research is needed. Clinicians should remain vigilant for medication side effects. The lack of association with this catalase variant doesn't rule out other genetic factors in ASD.

Small sample size (94 participants) from single population may limit generalizability. Laboratory findings in yeast cells may not directly translate to human responses. Study focused on only one genetic variant among many potentially relevant genes.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition influenced by genetic, epigenetic and environmental factors. Oxidative stress and antioxidant enzyme polymorphisms, particularly catalase (CAT), have been implicated in ASD, but findings remain inconsistent. In parallel, pharmacological interventions such as aripiprazole, which is widely used in ASD, have cellular toxicological profiles that remain incompletely defined. A total of 94 participants (39 ASD patients and 55 controls) were genotyped for the CAT polymorphism rs7943316 using tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR).

Genotype distributions were statistically compared using χand Fisher's exact tests. In vitro toxicological assays were performed in Saccharomyces cerevisiae wild type (BY4741) and mutant strains deficient in oxidative stress and lipid metabolism genes (CAT1, CPT2, PXA2 and FAA1). Yeast growth was quantified under increasing concentrations of aripiprazole, and ICvalues were determined. Genotype distribution of rs7943316 showed no significant difference between ASD and control groups (p = 0.866), indicating no association between this CAT polymorphism and ASD risk in this Lebanese cohort.

Toxicological profiling revealed that aripiprazole caused dose-dependent growth inhibition. Mutant strains lacking CAT1, CPT2 or PXA2 exhibited significantly reduced ICvalues compared to wild type (p < 0.05), highlighting oxidative stress detoxification, carnitine-mediated acetyl-CoA transport and peroxisomal fatty acid import as key determinants of drug sensitivity. CAT polymorphism rs7943316 is not associated with ASD in this population. However, aripiprazole exerts dose-dependent toxicity strongly modulated by oxidative stress and metabolic pathways.

These findings support the integration of genetic and toxicological approaches for understanding ASD and optimizing therapeutic safety.