Reference : Family-based association study on functional α-synuclein polymorphisms in attention-d...
Scientific journals : Article
Human health sciences : Neurology
Systems Biomedicine
http://hdl.handle.net/10993/41784
Family-based association study on functional α-synuclein polymorphisms in attention-deficit/hyperactivity disorder
English
Krüger, Rejko[University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Gerlach, Manfred[University Hospital of Würzburg, Würzburg, Germany > Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health]
Sharma, Manu[University of Tübingen, Tübingen, Germany > Center of Neurology and Hertie-Institute for Clinical Brain Research]
Romanos, Marcel[University Hospital of Würzburg, Würzburg, Germany > Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health]
Lech, Klaus Peter[University Hospital Würzburg, Würzburg, Germany > Division of Molecular Psychiatry, Center of Mental Health]
Walitza, Susanne[University of Zurich, Zurich, Switzerland > Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich]
Conzelmann, Annette H[University of Tübingen, Tübingen, Germany > Department for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy]
Renner, Tobias R[University of Tübingen, Tübingen, Germany > Department for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy]
[en] Studies have strongly suggested a disturbed regulation of dopaminergic neurotransmission in attention-deficit/hyperactivity disorder (ADHD) and Parkinson’s disease (PD). A genetic and phenotypic overlap between both disorders is discussed. A well-studied risk gene for PD is the gene coding for α-synuclein (SNCA). α-Synuclein, a protein located primarily in the presynaptic vesicles, has been suggested to play a role in the modulation of dopamine transporter (DAT) function. DAT is the target of psychostimulants for the treatment of ADHD and plays a key role in regulating the dopamine concentrations in the synaptic cleft. In our sample consisting of German families with children affected by ADHD, we tested for association of allelic variants of two functionally relevant polymorphisms of the α-synuclein gene (NACP-Rep1: 156 families, 232 children; rs356219: 195 families, 284 children) with ADHD. Transmission disequilibrium test analysis revealed no over-transmission for NACP-Rep1 (OR 1, pnom = 1 padj = 1) and rs356219 (OR 1.28; pnom = 0288) in affected siblings. However, a subanalysis on trios with index children showed a nominal association of rs356219 with ADHD (OR 1.43, pnom = 0.020), which survived Bonferroni correction (padj = 0.039); again, no association for NACP-Rep1 (OR 0.8, p = 0.317, padj = 0.634) was found. In conclusion, we found in our pilot study a trend for an association of the rs356219 genotype in SNCA that may affect α-synuclein function and contribute to the aetiology of ADHD. In light of the small sample size of our study, the link between PD and ADHD through dopamine-related neurobiology warrants further investigations. Future studies on SNCA in large ADHD samples should focus on specified symptoms and traits, e.g. attentional capacities or emotional dysregulation.
[University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
