VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome
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...
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doaj-644119809fa74b65bca6c7c90a8b34a52020-11-24T23:47:22ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532016-10-011010.3389/fnbeh.2016.00193204725VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndromeLaura Del Hoyo0Laura Del Hoyo1Laura Xicota2Laura Xicota3Laura Xicota4Klaus Langohr5Klaus Langohr6Gonzalo Sánchez-Benavides7Susana De Sola8Susana De Sola9Aida M Cuenca-Royo10Joan Rodriguez11Josep Rodriguez12Magi Farre13Mara Dierssen14Mara Dierssen15Mara Dierssen16Rafael De La Torre17Rafael De La Torre18Rafael De La Torre19Fundacion IMIMUniversidad Autónoma de BarcelonaFundacion IMIMCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyUniversidad Pompeu FabraFundacion IMIMUniversidad Politécnica de Barcelona/BarcelonaTechFundacion IMIMFundacion IMIMCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyFundacion IMIMFundacion IMIMFundacion IMIMFundacion IMIMCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and TechnologyUniversidad Pompeu FabraInstituto Salud Carlos IIIFundacion IMIMUniversidad Pompeu FabraInstituto Salud Carlos IIIDown 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 (AD)-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.http://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00193/fullDopamineDown SyndromePFC-dependent cognitionCOMTVal158MetVNTR-DAT1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura Del Hoyo Laura Del Hoyo Laura Xicota Laura Xicota Laura Xicota Klaus Langohr Klaus Langohr Gonzalo Sánchez-Benavides Susana De Sola Susana De Sola Aida M Cuenca-Royo Joan Rodriguez Josep Rodriguez Magi Farre Mara Dierssen Mara Dierssen Mara Dierssen Rafael De La Torre Rafael De La Torre Rafael De La Torre |
spellingShingle |
Laura Del Hoyo Laura Del Hoyo Laura Xicota Laura Xicota Laura Xicota Klaus Langohr Klaus Langohr Gonzalo Sánchez-Benavides Susana De Sola Susana De Sola Aida M Cuenca-Royo Joan Rodriguez Josep Rodriguez Magi Farre Mara Dierssen Mara Dierssen Mara Dierssen Rafael De La Torre Rafael De La Torre Rafael De La Torre VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome Frontiers in Behavioral Neuroscience Dopamine Down Syndrome PFC-dependent cognition COMTVal158Met VNTR-DAT1 |
author_facet |
Laura Del Hoyo Laura Del Hoyo Laura Xicota Laura Xicota Laura Xicota Klaus Langohr Klaus Langohr Gonzalo Sánchez-Benavides Susana De Sola Susana De Sola Aida M Cuenca-Royo Joan Rodriguez Josep Rodriguez Magi Farre Mara Dierssen Mara Dierssen Mara Dierssen Rafael De La Torre Rafael De La Torre Rafael De La Torre |
author_sort |
Laura Del Hoyo |
title |
VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome |
title_short |
VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome |
title_full |
VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome |
title_fullStr |
VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome |
title_full_unstemmed |
VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome |
title_sort |
vntr-dat1 and comtval158met genotypes modulate mental flexibility and adaptive behavior skills in down syndrome |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Behavioral Neuroscience |
issn |
1662-5153 |
publishDate |
2016-10-01 |
description |
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 (AD)-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. |
topic |
Dopamine Down Syndrome PFC-dependent cognition COMTVal158Met VNTR-DAT1 |
url |
http://journal.frontiersin.org/Journal/10.3389/fnbeh.2016.00193/full |
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