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

Metab Brain Dis. 2020 Feb;35(2):327-333. doi: 10.1007/s11011-019-00510-4. Epub 2019 Nov 14.

Abstract

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.

Keywords: Autism spectrum disorder (ASD); INFG; INFG-AS1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autism Spectrum Disorder / diagnosis
  • Autism Spectrum Disorder / genetics
  • Autism Spectrum Disorder / metabolism*
  • Case-Control Studies
  • Child
  • Female
  • Gene Expression
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / genetics
  • Male
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics

Substances

  • IFNG protein, human
  • RNA, Long Noncoding
  • Interferon-gamma