Dataset Information

Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder.

ABSTRACT: The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3'-UTR 9/10 VNTR, rs27072 in the 3'-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents' ratings) was associated with DAT1 intron8 (?p(2)=.063) and rs2283265 (?p(2)=.044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (?p(2)=.065) and depression (?p(2)=.059), and for DRD2 rs2283265, depression (?p(2)=.053). DRD2 rs2283265 was associated with teachers' global ratings of ADHD (?p(2)=.052). DAT1 intron8 was associated with parent-rated hyperactivity (?p(2)=.045) and both DAT1 9/10 VNTR (?p(2)=.105) and DRD2 rs2283265 (?p(2)=.069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples.

SUBMITTER: Gadow KD

PROVIDER: S-EPMC4084560 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder.

Gadow Kenneth D KD Pinsonneault Julia K JK Perlman Greg G Sadee Wolfgang W

Research in developmental disabilities 20140426 7

The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3'-UTR 9/10 VNTR, rs27072 in the 3'-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in ...[more]

PMID: 24780147

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Project description:DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

Dataset Information

Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder.

Publications

Association of dopamine gene variants, emotion dysregulation and ADHD in autism spectrum disorder.

Similar Datasets

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