The association between ST8SIA2 gene and behavioral phenotypes in children with autism spectrum disorder

Abstract

ObjectiveST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2) encodes a type II membrane protein that is thought to catalyze the transfer of sialic acid (SA) from CMP-SA to N-linked oligosaccharides and glycoproteins. Some population and animal studies have indicated an association between the ST8SIA2 gene and autism spectrum disorder (ASD). However, there is limited information on the correlation between ST8SIA2 and autistic behavioral symptoms.MethodsIn this study, 69 ASD and 76 normal control children who were age- and sex-matched were recruited. ST8SIA2 expression and methylation levels were measured by reverse transcription quantitative real-time PCR and pyrosequencing, respectively, and the behavioral phenotypes of ASD children were assessed.ResultsThe ASD group had lower ST8SIA2 gene expression levels than the control group [t(0.05/2,143) = 2.582, p = 0.011]. Moreover, ST8SIA2 expression levels were positively correlated with daily life skills (rs = 0.381, p = 0.008) and negatively associated with stereotyped behaviors in the ASD group (rs = -0.510, p = 0.004). The methylation levels of the Chr. 15: 92984625 and Chr. 15: 92998561 sites of the ST8SIA2 gene in ASD children were higher than those of controls. The Chr. 15: 92984625 site was positively correlated with the stereotyped behaviors of ASD children (rs = 0.41, p = 0.039).ConclusionThis study provides a scientific basis to elucidate the relationship between the ST8SIA2 gene and behavioral phenotypes of ASD.

DNA Methylation Biomarkers for Young Children with Idiopathic Autism Spectrum Disorder: A Systematic Review

“…In addition to disease severity, peripheral blood DNA methylation has been associated with the behavioral phenotypes of ASD. Indeed, the methylation of a CpG site of the ST8SIA2 gene has been found to positively correlate with stereotyped behaviors [49], while the methylation of TGFB1 was found to positively correlate with the interaction ability score [50]. Although the results of these studies are of great interest, as they suggest that peripheral DNA methylation could provide biomarkers to detect different levels of expression of the ASD spectrum, they need to be replicated in further studies.…”

“…Increased methylation of the NCAM1 gene was observed in the peripheral blood of ASD children when compared to TD individuals, as well as increased NGF gene methylation levels in ASD with neurodevelopmental regression when compared to both TD and ASD without regression [39]. By using pyrosequencing, increased methylation of the ST8SIA2 gene was observed in the peripheral blood of ASD compared to TD children [49]. In two reports, gene-specific DNA methylation was evaluated by means of MS-HRM [31,40].…”

Alterations in the Glycan Composition of Serum Glycoproteins in Attention-Deficit Hyperactivity Disorder

“…They concluded that there was a possibility of using SA as a biomarker for ASD. The mentioned research group later focused on the connection between neural cell adhesion molecules [38] and the gene ST8SIA1 [39] with ASD, as they were both downregulated in ASD patients. Another group found an additional decrease in SA levels in the saliva of ASD patients and the potential impact of SA levels on the hyperactivity of ASD patients [40].…”

Therapeutic potential to target sialylation and SIGLECs in neurodegenerative and psychiatric diseases

“…In children with autism spectrum disorder, ST8SIA2 gene expression levels were decreased compared to age- and sex-matched controls. Thereby, ST8SIA2 gene expression levels negatively correlated with the childhood autism rating scale (CARS) score, indicating more serious stereotype behaviors and sensory abnormalities with decreasing ST8SIA2 expression ( 107 ). Furthermore, a correlation between polysialic acid serum levels and structural brain changes related to the schizophrenia spectrum and bipolar disorder was observed, suggesting that soluble polysialic acid, released as part of the disease process in the brain, can be detected in the patients’ serum ( 109 ).…”