Single Nucleotide Polymorphisms in Oxidative Stress-Related Genes Are Associated with Autism Spectrum Disorders

Area of Science:

• Genetics and Molecular Biology
• Neuroscience
• Biochemistry

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social-communication deficits and repetitive behaviors.
• The etiology of ASD is multifactorial, involving genetic and environmental influences.
• Oxidative stress, an imbalance between reactive oxygen species and antioxidant defenses, has been implicated in various neurodevelopmental disorders.

Purpose of the Study:

• To investigate the genetic predisposition to oxidative response in individuals with ASD.
• To explore the relationship between specific gene polymorphisms involved in detoxification and oxidative stress pathways and ASD.
• To assess oxidative stress markers and DNA damage in ASD patients.

Main Methods:

• Genomic DNA was extracted from lymphocytes of 106 ASD patients and 90 healthy controls.
• Genotyping was performed using real-time PCR and electrophoresis to analyze GST deletion variants.
• Oxidative stress markers (dROMs, BAP, AOPP) and DNA damage (Single Cell Gel Electrophoresis) were measured.

Main Results:

• ASD patients exhibited a mild oxidative stress status and increased DNA damage in lymphocyte nuclei compared to controls.
• Significant associations were identified between ASD and polymorphisms in genes related to detoxification and oxidative stress response.
• Specific GST deletion variants were found to be associated with ASD.

Conclusions:

• Genetic factors influencing oxidative stress response and detoxification pathways play a role in the susceptibility to ASD.
• Oxidative stress markers and DNA damage are altered in individuals with ASD.
• A multimodal approach is essential for managing ASD, potentially incorporating strategies to address oxidative stress.