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.
KeywordsAutism spectrum disorder (ASD) INFG INFG-AS1
The present study was supported by a grant from Shahid Beheshti University of Medical Sciences (grant number: 14254).
Compliance with ethical standards
Conflict of interest
The authors declare that have no conflict of interest.
- AbuHashim HM (2013) Association between plasma levels of transforming growth factor-b1, IL-23 and IL-17 and the severity of autism in Egyptian children. Elsevier Ltd. 7Google Scholar
- Ashwood P, Enstrom A, Krakowiak P, Hertz-Picciotto I, Hansen RL, Croen LA, Ozonoff S, Pessah IN, Van De Water JJJON (2008) Decreased transforming growth factor Beta1 in autism: a potential link between immune dysregulation and impairment in clinical behavioral outcomes. J Neuroimmunol 204:149–153PubMedPubMedCentralCrossRefGoogle Scholar
- Dorahy MJ (2014) The Diagnostic and Statistical Manual of Mental Disorders–5th edition (DSM-5)Google Scholar
- Fombonne EJRDIAR (2005) In: Casanova Mf (ed) The epidemiology of pervasive developmental disorders, pp 1–25Google Scholar
- Inoue R, Sakaue Y, Sawai C, Sawai T, Ozeki M, Romero-Pérez GA, Tsukahara TJB (2016) A preliminary investigation on the relationship between gut microbiota and gene expressions in peripheral mononuclear cells of infants with autism Spectrum disorders. Biosci Biotechnol Biochem 80:2450–2458PubMedCrossRefGoogle Scholar
- Padua D, Mahurkar-Joshi S, Law IKM, Polytarchou C, Vu JP, Pisegna JR, Shih D, Iliopoulos D, Pothoulakis CJAJOP-G, Physiology, L. (2016) A Long noncoding Rna signature for ulcerative colitis identifies Ifng-As1 as an enhancer of inflammation. Am J Physiol Gastrointest Liver Physiol 311:G446–G457PubMedPubMedCentralCrossRefGoogle Scholar
- Shaw C, Sheth S, Li D, Tomljenovic LJOA (2014) Etiology of autism Spectrum disorders: genes, environment, or both. OA Autism 2:11Google Scholar
- Tager-Flusberg H, Paul R, Lord CJHOA & Disorders, P. D. (2005) Language and communication in autism, vol 1, pp 335–364Google Scholar