IFNG/IFNG-AS1 expression level balance: implications for autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with different epidemiological, genetic, epigenetic, and environmental factors. Although its etiology is not fully understood, immune dysfunction is implicated in this disease. Recently, a large number of genes encoding long noncoding RNAs (lncRNAs) were discovered which act as positive or negative regulators of neighboring target genes. The lncRNA, Interferon gamma-antisense RNA (IFNG-AS1), regulates expression levels of the Interferon gamma (IFNG) gene. In the present study, we investigated expression of IFNG and IFNG-AS1 in 50 children with ASD (15 females and 35 males, mean age: 6 +/- 1.4 years) and 50 healthy controls (14 females and 36 males, mean age: 6 +/- 1.74 years) by real time PCR technique. The results showed significant up-regulation of IFNG and down-regulation of IFNG-AS1 expression in children with ASD compared to controls (Fold change=1.5, P<0.0001; Fold change=-0.143, P=0.013, respectively). The IFNG expression level increase was more pronounced in male ASD children (Fold change=1.621; p<0.0001). Our data reveal a functional disruption in the interactive network of IFNG/IFNG-AS1 regulation, which could be a contributing factor in the chronic inflammatory aspect of ASD. Our findings can help understanding the underlying contributors to ASD pathogenesis and find novel treatment options for children with ASD.