Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders

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Muiños-Gimeno M, Guidi M, Kagerbauer B, Martín-Santos R, Alonso P, Menchón J M, Gratacòs M, Estivill X, Espinosa-Parrilla Y. Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders. Human Mutation. 2009; 30(7): 1062-1071. DOI 10.1002/humu.21005
http://hdl.handle.net/10230/16310
To cite or link this document: http://hdl.handle.net/10230/16310
dc.contributor.author Muiños Gimeno, Margarita
dc.contributor.author Guidi, Mònica
dc.contributor.author Kagerbauer, Birgit
dc.contributor.author Martín Santos, Rocío
dc.contributor.author Navinés, Ricard
dc.contributor.author Alonso, Pino
dc.contributor.author Menchón, José M.
dc.contributor.author Gratacós Mayora, Mònica
dc.contributor.author Estivill, Xavier
dc.contributor.author Espinosa Parrilla, Yolanda
dc.date.accessioned 2012-03-15T09:19:19Z
dc.date.available 2012-03-15T09:19:19Z
dc.date.issued 2009
dc.identifier.citation Muiños-Gimeno M, Guidi M, Kagerbauer B, Martín-Santos R, Alonso P, Menchón J M, Gratacòs M, Estivill X, Espinosa-Parrilla Y. Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders. Human Mutation. 2009; 30(7): 1062-1071. DOI 10.1002/humu.21005
dc.identifier.issn 1059-7794
dc.identifier.uri http://hdl.handle.net/10230/16310
dc.description.abstract Genetic and functional data indicate that variation in the expression of the neurotrophin-3 receptor gene (NTRK3) may have an impact on neuronal plasticity, suggesting a role for NTRK3 in the pathophysiology of anxiety disorders. MicroRNA (miRNA) posttranscriptional gene regulators act by base-pairing to specific sequence sites, usually at the 3'UTR of the target mRNA. Variants at these sites might result in gene expression changes contributing to disease susceptibility. We investigated genetic variation in two different isoforms of NTRK3 as candidate susceptibility factors for anxiety by resequencing their 3'UTRs in patients with panic disorder (PD), obsessive-compulsive disorder (OCD), and in controls. We have found the C allele of rs28521337, located in a functional target site for miR-485-3p in the truncated isoform of NTRK3, to be significantly associated with the hoarding phenotype of OCD. We have also identified two new rare variants in the 3'UTR of NTRK3, ss102661458 and ss102661460, each present only in one chromosome of a patient with PD. The ss102661458 variant is located in a functional target site for miR-765, and the ss102661460 in functional target sites for two miRNAs, miR-509 and miR-128, the latter being a brain-enriched miRNA involved in neuronal differentiation and synaptic processing. Interestingly, these two variants significantly alter the miRNA-mediated regulation of NTRK3, resulting in recovery of gene expression. These data implicate miRNAs as key posttranscriptional regulators of NTRK3 and provide a framework for allele-specific miRNA regulation of NTRK3 in anxiety disorders.
dc.description.sponsorship This work was supported by the “Instituto Carlos III and Fondo de Investigaciones Sanitarias” [CIBER-CB06/02/0058, CIBER-SAM, FIS/ISCIII:P1052565, ISCIII:GO3/184], the “Fundació la Marató-TV3” [014331], the “Departament d’Universitats Innovació i Empresa, Generalitat de Catalunya” [2005SGR00008] and the European Union Sixth Framework Programme Integrated Project SIROCCO [Grant LSHG-CT-2006-037900]. The Spanish National Genotyping Center (CeGen) is supported by “Genoma España” and the “Ministerio de Educación y Ciencia” (Spanish Government). M.M is a recipient of a FIS fellowship [FI05/0006]. Y.E was supported by the “Ramón y Cajal” Program [Spanish Ministry of Science and Education]. We would like to thank J.M. Mercader for his help in technical issues and suggestions as well as B. Cormand, A. Macaya, R. Corominas and E. Cuenca (Hospital Universitari Vall d'Hebron, Barcelona) for kindly proving us with control samples.
dc.language.iso eng
dc.publisher Wiley-Blackwell
dc.relation.ispartof Human Mutation. 2009; 30(7): 1062-1071
dc.rights (c) 2009 WILEY-LISS, INC. This is the pre-peer reviewed version of the following article: Muiños-Gimeno M, Guidi M, Kagerbauer B, Martín-Santos R, Alonso P, Menchón J M, Gratacòs M, Estivill X, Espinosa-Parrilla Y. Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders. Human Mutation. 2009; 30(7): 1062-1071. DOI 10.1002/humu.21005, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/humu.21005/pdf
dc.subject.other Genètica humana -- Variació
dc.subject.other Interaccions ARN-proteïnes
dc.subject.other Neurosi d'angoixa -- Aspectes genètics
dc.title Allele variants in functional MicroRNA target sites of the neurotrophin-3 receptor gene (NTRK3) as susceptibility factors for anxiety disorders
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1002/humu.21005
dc.subject.keyword Functional allele variant
dc.subject.keyword SNP
dc.subject.keyword NTRK3
dc.subject.keyword microRNA
dc.subject.keyword Posttranscriptional regulation
dc.subject.keyword Anxiety disorder
dc.subject.keyword Obsessive compulsive disorder
dc.subject.keyword Panic disorder
dc.subject.keyword Hoarding
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/submittedVersion


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