Potential for diagnosis versus therapy monitoring of attention deficit hyperactivity disorder: a new epigenetic biomarker interacting with both genotype and auto-immunity
| Autor: | Mariangela Pucci, Oleg Granstrem, Claudio D'Addario, Luca Cerniglia, Silvia Cimino, Paolo Curatolo, Giovanni Laviola, Walter Adriani, Esterina Pascale, Renata Tambelli, Emilia Romano, Mauro Maccarrone |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology Untranslated region Male medicine.medical_specialty Adolescent Genotype 03 medical and health sciences 0302 clinical medicine Internal medicine Conners’ scales mental disorders Developmental and Educational Psychology medicine CGAS scale Attention deficit hyperactivity disorder Humans Allele Child 10-Repeat allele Dopamine transporter Genetics 9-Repeat allele Polymorphism Genetic biology OCD Auto-antibodies (aAbs) to neuro-receptors General Medicine medicine.disease Settore MED/39 - Neuropsichiatria Infantile Psychiatry and Mental health Variable number tandem repeat 030104 developmental biology nervous system CpG site Attention Deficit Disorder with Hyperactivity Dopamine transporter (DAT) Epigenetics in neuro-psychiatry Tourette’s Pediatrics Perinatology and Child Health biology.protein Biomarker (medicine) Female Psychology 030217 neurology & neurosurgery attention deficit disorder with hyperactivity genes transporter gene |
| Popis: | In view of the need for easily accessible biomarkers, we evaluated in ADHD children the epigenetic status of the 5'-untranslated region (UTR) in the SLC6A3 gene, coding for human dopamine transporter (DAT). We analysed buccal swabs and sera from 30 children who met DSM-IV-TR criteria for ADHD, assigned to treatment according to severity. Methylation levels at six-selected CpG sites (among which, a CGGCGGCGG and a CGCG motif), alone or in combination with serum titers in auto-antibodies against dopamine transporter (DAT aAbs), were analysed for correlation with CGAS scores (by clinicians) and Conners' scales (by parents), collected at recruitment and after 6 weeks. In addition, we characterized the DAT genotype, i.e., the variable number tandem repeat (VNTR) polymorphisms at the 3'-UTR of the gene. DAT methylation levels were greatly reduced in ADHD patients compared to control, healthy children. Within patients carrying at least one DAT 9 allele (DAT 9/x), methylation at positions CpG2 and/or CpG6 correlated with recovery, as evident from delta-CGAS scores as well as delta Conners' scales ('inattentive' and 'hyperactive' subscales). Moreover, hypermethylation at CpG1 position denoted severity, specifically for those patients carrying a DAT 10/10 genotype. Intriguingly, high serum DAT-aAbs titers appeared to corroborate indications from high CpG1 versus high CpG2/CpG6 levels, likewise denoting severity versus recovery in DAT 10/10 versus 9/x patients, respectively. These profiles suggest that DAT 5'UTR epigenetics plus serum aAbs can serve as suitable biomarkers, to confirm ADHD diagnosis and/or to predict the efficacy of treatment. |
| Databáze: | OpenAIRE |
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