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In this study, we aimed at evaluating gene expression changes induced by acute cocaine exposure on SH-SY5Y-differentiated cells, which have been widely used as a dopaminergic neuronal model. Expression changes and a concomitant increase in neuronal activity were observed after a 5 \u03bc<jats:sc>M<\/jats:sc> cocaine exposure, whereas no changes in gene expression or in neuronal activity took place at 1\u2009\u03bc<jats:sc>M<\/jats:sc> cocaine. Changes in gene expression were identified in a total of 756 genes, mainly related to regulation of transcription and gene expression, cell cycle, adhesion and cell projection, as well as mitogen-activeated protein kinase (MAPK), CREB, neurotrophin and neuregulin signaling pathways. Some genes displaying altered expression were subsequently targeted with predicted functional single-nucleotide polymorphisms (SNPs) in a case\u2013control association study in a sample of 806 cocaine-dependent patients and 817 controls. This study highlighted associations between cocaine dependence and five SNPs predicted to alter microRNA binding at the 3\u2032-untranslated region of the <jats:italic>NFAT5<\/jats:italic> gene. The association of SNP rs1437134 with cocaine dependence survived the Bonferroni correction for multiple testing. A functional effect was confirmed for this variant by a luciferase reporter assay, with lower expression observed for the rs1437134G allele, which was more pronounced in the presence of hsa-miR-509. However, brain volumes in regions of relevance to addiction, as assessed with magnetic resonance imaging, did not correlate with <jats:italic>NFAT5<\/jats:italic> variation. These results suggest that the <jats:italic>NFAT5<\/jats:italic> gene, which is upregulated a few hours after cocaine exposure, may be involved in the genetic predisposition to cocaine dependence.<\/jats:p>","DOI":"10.1038\/tp.2015.158","type":"journal-article","created":{"date-parts":[[2015,10,27]],"date-time":"2015-10-27T17:09:17Z","timestamp":1445965757000},"page":"e667-e667","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence"],"prefix":"10.1038","volume":"5","author":[{"given":"N","family":"Fern\u00e0ndez-Castillo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Cabana-Dom\u00ednguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Soriano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"S\u00e0nchez-Mora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Roncero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Grau-L\u00f3pez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"Ros-Cucurull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Daigre","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M M J","family":"van Donkelaar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Franke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Casas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Ribas\u00e9s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B","family":"Cormand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,10,27]]},"reference":[{"key":"BFtp2015158_CR1","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1038\/386827a0","volume":"386","author":"ND Volkow","year":"1997","unstructured":"Volkow ND, Wang GJ, Fischman MW, Foltin RW, Fowler JS, Abumrad NN et al. 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