VNTR-DAT1 and COMTVal158Met Genotypes Modulate Mental Flexibility and Adaptive Behavior Skills in Down Syndrome
| Autor: | Ester Civit, Laura del Hoyo, Aida Cuenca-Royo, Laia Roca, Henri Bléhaut, Joan Rodríguez, Jesús Pujol, Magí Farré, Gonzalo Sánchez-Benavides, Judit Sánchez, Alessandro Principe, Jordi Peña-Casanova, Susana Solá, Rut Freixas, Silvina Catuara-Solarz, Bessy Benejam, Jose Rodríguez-Morató, Josep Ma Espadaler, Gimena Hernandez, Rafael de la Torre, Sebastià Videla, Klaus Langohr, Valérie Legout, Laura Blanco, Iván Dueñas, Magí Farr, Laura Xicota, Mara Dierssen, Katy Trias |
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| Přispěvatelé: | Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. GRBIO - Grup de Recerca en Bioestadística i Bioinformàtica |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Down syndrome Biomatemàtica Cognitive Neuroscience Dopamine Population Matemàtiques i estadística::Matemàtica aplicada a les ciències [Àrees temàtiques de la UPC] 92 Biology and other natural sciences::92D Genetics and population dynamics [Classificació AMS] 62 Statistics::62D05 Sampling theory sample surveys [Classificació AMS] lcsh:RC321-571 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Genotype medicine Dementia PFC-dependent cognition Allele Sampling (Statistics) Prefrontal cortex education COMTVal158Met lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Genetics Adaptive behavior Biomathematics education.field_of_study Matemàtiques i estadística::Estadística aplicada::Estadística biosanitària [Àrees temàtiques de la UPC] Cognitive flexibility medicine.disease 030104 developmental biology Neuropsychology and Physiological Psychology VNTR-DAT1 Psychology Mostreig (Estadística) 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | Frontiers in Behavioral Neuroscience Frontiers in Behavioral Neuroscience, Vol 10 (2016) Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname UPCommons. Portal del coneixement obert de la UPC Universitat Politècnica de Catalunya (UPC) |
| Popis: | Down syndrome (DS) is an aneuploidy syndrome that is caused by trisomy for human chromosome 21 resulting in a characteristic cognitive and behavioral phenotype, which includes executive functioning and adaptive behavior difficulties possibly due to prefrontal cortex (PFC) deficits. DS also present a high risk for early onset of Alzheimer Disease-like dementia. The dopamine (DA) system plays a neuromodulatory role in the activity of the PFC. Several studies have implicated trait differences in DA signaling on executive functioning based on genetic polymorphisms in the genes encoding for the catechol-O-methyltransferase (COMTVal158Met) and the dopamine transporter (VNTR-DAT1). Since it is known that the phenotypic consequences of genetic variants are modulated by the genetic background in which they occur, we here explore whether these polymorphisms variants interact with the trisomic genetic background to influence gene expression, and how this in turn mediates DS phenotype variability regarding PFC cognition. We genotyped 69 young adults of both genders with DS, and found that VNTR-DAT1 was in Hardy-Weinberg equilibrium but COMTVal158Met had a reduced frequency of Met allele homozygotes. In our population, genotypes conferring higher DA availability, such as Met allele carriers and VNTR-DAT1 10-repeat allele homozygotes, resulted in improved performance in executive function tasks that require mental flexibility. Met allele carriers showed worse adaptive social skills and self-direction, and increased scores in the social subscale of the Dementia Questionnaire for People with Intellectual Disabilities than Val allele homozygotes. The VNTR-DAT1 was not involved in adaptive behavior or early dementia symptoms. Our results suggest that genetic variants of COMTVal158Met and VNTR-DAT1 may contribute to PFC-dependent cognition, while only COMTVal158Met is involved in behavioral phenotypes of DS, similar to euploid population. This work was supported by grants, donations and agreements from Fondation Jérôme Lejeune (Paris, France), Instituto de Salud Carlos III FEDER, (PI11/00744), MINECO (SAF2010-19434 and SAF2013-49129-C2-1-R), EU (Era Net Neuron PCIN-2013-060), DIUE de la Generalitat de Catalunya (SGR 2009/1450, 2014SGR 680, 2014 SGR 464, SGR 2009/718, and SGR 2014/1125). LdH is recipient of a pre-doctoral fellowship from ISCIII [FI12/00319]. CRG is Center of Excellence Severo Ochoa SEV-2012-0208. |
| Databáze: | OpenAIRE |
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