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Achalasia can be considered a multifactorial disorder as it occurs in related individuals and is associated with HLA class II genes, thereby suggesting genetic influence. We used microarray technology and advanced <jats:italic>in-silico<\/jats:italic> functional analyses to perform the first genome-wide expression profiling of mRNA in tissue samples from 12 achalasia and 5 control patients. It revealed 1,728 differentially expressed genes, of these, 837 (48.4%) were up-regulated in cases. In particular, genes participating to the <jats:italic>smooth muscle contraction<\/jats:italic> biological function were mostly up-regulated. Functional analysis revealed a significant enrichment of neuronal\/muscular and neuronal\/immunity processes. Upstream regulatory analysis of 180 genes involved in these processes suggested <jats:italic>TLR4<\/jats:italic> and <jats:italic>IL18<\/jats:italic> as critical key-players. Two functional gene networks were significantly over-represented: one involved in <jats:italic>organ morphology, skeletal muscle system development and function and neurological diseases<\/jats:italic> and the other participating in <jats:italic>cell morphology, humoral immune response and cellular movement<\/jats:italic>. These results highlight on pivotal genes that may play critical roles in neuronal\/muscular and neuronal\/immunity processes and that may contribute to the onset and development of achalasia.<\/jats:p>","DOI":"10.1038\/srep31549","type":"journal-article","created":{"date-parts":[[2016,8,11]],"date-time":"2016-08-11T09:50:45Z","timestamp":1470909045000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia"],"prefix":"10.1038","volume":"6","author":[{"given":"Orazio","family":"Palmieri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Mazza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Merla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Fusilli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Cuttitta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Martino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Latiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Corritore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Bossa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orazio","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia Anna","family":"Muscarella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Carella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Graziano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Andriulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Latiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,8,11]]},"reference":[{"key":"BFsrep31549_CR1","doi-asserted-by":"crossref","first-page":"5806","DOI":"10.3748\/wjg.v19.i35.5806","volume":"19","author":"OM O\u2019Neill","year":"2013","unstructured":"O\u2019Neill, O. 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