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Título

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

AutorMuiños-Gimeno, Margarita; Espinosa-Parrilla, Yolanda ; Sigrid Juselius Foundation
Palabras claveAnxiety
Association study
Candidate gene
MicroRNAs
Panic disorder
Postranscriptional regulation
Fecha de publicación17-dic-2010
EditorElsevier
CitaciónBiological Psychiatry 69(6) : 526–533 (2011)
Resumen[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.
DescripciónDisponible desde www.ncbi.nlm.nih.gov. -- Autores: Muiños-Gimeno, Margarita ... [et al.]
Versión del editorhttp://dx.doi.org/10.1016/j.biopsych.2010.10.010
URIhttp://hdl.handle.net/10261/50548
DOI10.1016/j.biopsych.2010.10.010
ISSN0006-3223
E-ISSN1873-2402
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