Association between the methylation of six apoptosis‑associated genes with autism spectrum disorder

Abstract

Excessive apoptosis hinders the process of brain maturation and is regarded as one of the principal risk factors for the development of autism spectrum disorder (ASD). The aim of the present study was to investigate the association between the methylation of six apoptosis‑associated genes [transforming growth factor β 1 (TGFB1), BCL2 associated X, apoptosis regulator, insulin like growth factor binding protein 3, protein kinase C β 1, presenilin 2 and C‑C motif chemokine ligand 2] and ASD. Using quantitative methylation‑specific polymerase chain reaction technology, DNA methylation levels were detected in 42 autistic and 26 control subjects. The logistic regression analysis results demonstrated that of the six genes, only TGFB1 was significantly hypomethylated in peripheral blood samples from children with autism compared with control samples (mean percentage of methylated reference, 0.011% vs. 0.019%; age‑adjusted P=0.028). In addition, TGFB1 methylation was identified to be positively associated with the interaction ability score from the Autism Behavior Checklist (r=0.452; P=0.035). These data suggested that decreased TGFB1 methylation may contribute to the development 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.…”

“…In that study, a higher frequency of OXTR promoter hypomethylation was observed in the peripheral blood of 27 ASD individuals compared to 39 TD individuals [37]. The qMSP technique was used in two studies [42,50]. Hu et al investigated methylation levels of the HTR4 gene in the peripheral blood of 61 ASD children and 66 TD children, and decreased methylation was observed in the ASD individuals.…”

“…Moreover, higher methylation was observed in female ASD individuals than in male ASD individuals, while the gender difference was not significant in TD subjects [42]. Zhao et al investigated the methylation patterns of TGFB1, BAX, IGFBP3, PRKCB, PSEN2, and CCL2 in the peripheral blood of 42 ASD patients and 26 TD patients, finding that the rate of the methylation of TGFB1 was decreased in ASD and was positively associated with the interaction ability score [50]. One study used the BSP technique to investigate the methylation levels of the ESR2 gene in the peripheral blood of 54 ASD and 54 TD individuals, observing that 8 CpG sites in the ESR2 5 -flanking region were hypermethylated in ASD subjects and that 4 CpG sites were positively associated with the severity of the symptoms [48].…”

Analysis of lncRNA, miRNA, mRNA-associated ceRNA networks in Autism

“…These three isoforms are expressed in several central nervous system CNS cell types including neurons, astrocytes, and microglia [3]. In the past, it has been observed that the expression level of TGFB1 in the plasma of autistic children is significantly reduced [23]. The MAPK pathway regulates neural progenitor biogenesis, learning and memory, and mRNA translation by phosphorylation of TSC2 and eIF4E through MAPK-interacting kinase 1 and 2 (MNK1 and MNK2).…”

Atualização Em Transtorno Do Espectro Autista: Da Suspeita Ao Diagnóstico No Gênero Feminino

“…Além disso, dentre os seis genes associados à apoptose, a sinalização do TGFB1 pode ser comprometida no TEA, por meio de uma hipometilação significativa, tendo assim uma consequência cognitiva secundária associada ao transtorno (ZHAO et al, 2018). Não somente a hipometilação, mas também a hipermetilação pode contribuir para deficiências cognitivas, como a hipermetilação nas regiões promotoras de codificação (ilhas CpG do tipo 16) sendo possível causa de déficits mais pronunciados na teoria da mente e na autoconsciência.…”