title: Gene expression of muscular and neuronal pathways is cooperatively dysregulated in patients with idiopathic achalasia.
abstract: Idiopathic achalasia is characterized by the absence of peristalsis secondary to loss of neurons in the myenteric plexus that hampers proper relaxation of the lower esophageal sphincter. 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 in-silico 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 smooth muscle contraction 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 TLR4 and IL18 as critical key-players. Two functional gene networks were significantly over-represented: one involved in organ morphology, skeletal muscle system development and function, and neurological diseases, and the other participating in cell morphology, humoral immune response and cellular movement. 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.
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Orazio
authors: O
authors: Palmieri
authors: Bioinformatics Unit, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Tommaso
authors: T
authors: Mazza
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Antonio
authors: A
authors: Merla
authors: Bioinformatics Unit, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Caterina
authors: C
authors: Fusilli
authors: Unit of General Surgery 2nd and Thoracic Surgery, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Antonello
authors: A
authors: Cuttitta
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Giuseppina
authors: G
authors: Martino
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Tiziana
authors: T
authors: Latiano
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Giuseppe
authors: G
authors: Corritore
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Fabrizio
authors: F
authors: Bossa
authors: Medical Genetics Service, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Orazio
authors: O
authors: Palumbo
authors: Laboratory of Oncology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Lucia Anna
authors: LA
authors: Muscarella
authors: Medical Genetics Service, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Massimo
authors: M
authors: Carella
authors: Pathology Unit, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Paolo
authors: P
authors: Graziano
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Angelo
authors: A
authors: Andriulli
authors: Division of Gastroenterology, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia, Italy.
authors: Anna
authors: A
authors: Latiano
mesh_terms: D000328:Adult; D000368:Aged; D004931:Esophageal Achalasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D009197:Myenteric Plexus / Q000378:metabolism* / Q000473:pathology
chemical_list: D006680:HLA Antigens