An Association study of the SOD2 rs4880 (Ala16Val) Variant with Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a complex and highly heterogeneous neurodevelopmental disorder. Among various contributing factors, oxidative stress plays a major role in ASD pathophysiology. The study of antioxidant genes, therefore, may contribute to revealing important aspects of ASD. The Superoxide Dismutase (SOD) gene family (well-known antioxidant) plays a crucial role in protecting cells from oxidative damage. This study aimed to investigate the functional impact of the SOD2 rs4880 (C>T) variant in children with ASD. A total of 595 participants were recruited, including 366 children with ASD (295 males and 71 females) and 229 healthy controls (125 males and 104 females). Genotyping was performed by the ARMS-PCR method. The trait severity of ASD was evaluated by the Childhood Autism Rating Scale, 2nd edition (CARS2-ST). SOD2 gene expression was measured by quantitative real-time PCR in a subset of 99 ASD probands and 66 controls. Our findings revealed a significant association between rs4880 and ASD, with a higher frequency of the T allele and TT genotype among ASD subjects than among controls. Differences in SOD2 gene expression were observed between ASD subjects and controls across rs4880 genotype groups, suggesting that rs4880 variation may influence SOD2 expression. Furthermore, reduced SOD2 expression was associated with increased behavioural symptoms, particularly "Fear or Nervousness" and impaired "Verbal Communication," indicating a potential relationship between altered antioxidant defence and specific behavioural manifestations of ASD. These findings suggest that the SOD2 rs4880 variant may contribute to ASD susceptibility through its association with altered SOD2 expression and behavioural characteristics.