1. Human microRNAs miR-22 miR-138-2 miR-148a and miR-488 Are Associated with Panic Disorder and Regulate Several Anxiety Candidate Genes and Related Pathways
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Laura Kananen, Kristi Pettai, Tessa Sipilä, Ricard Navinés, Eduard Maron, Birgit Kagerbauer, Margarita Muiños-Gimeno, Xavier Estivill, Yolanda Espinosa-Parrilla, Iiris Hovatta, Mònica Gratacòs, Rocío Martín-Santos, Monica Guidi, Andres Metspalu, Instituto de Salud Carlos III, Fundació La Marató de TV3, Generalitat de Catalunya, Ministerio de Ciencia e Innovación (España), European Commission, Estonian Government, Fundación Genoma España, Academy of Finland, Yrjo and Tuulikki Ilvonen Foundation, and Estonian Science Foundation
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Candidate gene ,Anxiety ,Candidate genes ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,microRNA ,medicine ,Gene silencing ,Biological Psychiatry ,030304 developmental biology ,Genetics ,0303 health sciences ,Panic disorder ,Panic ,medicine.disease ,Postranscriptional regulation ,3. Good health ,Association study ,MicroRNAs ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery ,Anxiety disorder - Abstract
Disponible desde www.ncbi.nlm.nih.gov. -- Autores: Muiños-Gimeno, Margarita ... [et al.], [Background] The involvement of microRNAs (miRNAs) in neuronal differentiation and synaptic plasticity suggests a role for miRNAs in psychiatric disorders; association analyses and functional approaches were used to evaluate the implication of miRNAs in the susceptibility for panic disorder., [Methods] Case-control studies for 712 single-nucleotide polymorphisms (SNPs) tagging 325 human miRNA regions were performed in 203 Spanish patients with panic disorder and 341 control subjects. A sample of 321 anxiety patients and 642 control subjects from Finland and 102 panic disorder patients and 829 control subjects from Estonia was used as a replica. Reporter-gene assays and miRNA overexpression experiments in neuroblastoma cells were used to functionally evaluate the spectrum of genes regulated by the associated miRNAs., [Results] Two SNPs associated with panic disorder: rs6502892 tagging miR-22 (p < .0002), and rs11763020 tagging miR-339 (p < .00008). Other SNPs tagging miR-138-2, miR-488, miR-491, and miR-148a regions associated with different panic disorder phenotypes. Replication in the north-European sample supported several of these associations, although they did not pass correction for multiple testing. Functional studies revealed that miR-138-2, miR-148a, and miR-488 repress (30%–60%) several candidate genes for panic disorder—GABRA6, CCKBR and POMC, respectively—and that miR-22 regulates four other candidate genes: BDNF, HTR2C, MAOA, and RGS2. Transcriptome analysis of neuroblastoma cells transfected with miR-22 and miR-488 showed altered expression of a subset of predicted target genes for these miRNAs and of genes that might be affecting physiological pathways related to anxiety., [Conclusions] This work represents the first report of a possible implication of miRNAs in the etiology of panic disorder., Este trabajo fue financiado por el "Instituto Carlos III y el Fondo de Investigaciones Sanitarias" (nº CIBER-CB06/02/0058, CIBER-SAM, FIS/ISCIII: P1052565, ISCIII: GO3/184, FI05/0006 para Margarita Muiños-Gimeno), la "Fundación Marató-TV3" (nº 014 331), el "Departament d'Universitats Innovació i Empresa, Generalitat de Catalunya" (nº 2005SGR00008 y 2009SGR1435), el Ministerio de Ciencia e Innovación (nº SAF2008-00357), Sexto Programa Marco de la Unión Europea Proyecto Integrado SIROCCO (nº LSHG-CT-2006-037900). Andres Metspalu fue apoyado por el Séptimo Programa Marco Unión de la Europea (nº ENGAGE 201413, ECOGENE # 205419 EBC, y OPENGENE # 245536), la Unión Europea a través del Fondo Europeo de Desarrollo Regional (Centro de Excelencia en Genómica) y el Gobierno de Estonia (nº SF0180142s08). El Centro Español Nacional de Genotipado (CeGen) fue apoyado por "Genoma España". Academia de Finlandia, Yrjö and Tuulikki Ilvonen Foundation y la Fundación Sigrid Juselius. Fundación Científica de Estonia (nº 7034).
- Published
- 2011
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