title: Crohn's Disease Localization Displays Different Predisposing Genetic Variants.
abstract: BACKGROUND
  Crohn's disease (CD) is a pathologic condition with different clinical expressions that may reflect an interplay between genetics and environmental factors. Recently, it has been highlighted that three genetic markers, NOD2, MHC and MST1, were associated to distinct CD sites, supporting the concept that genetic variations may contribute to localize CD. Genetic markers, previously shown to be associated with inflammatory bowel disease (IBD), were tested in CD patients with the aim to better dissect the genetic relationship between ileal, ileocolonic and colonic CD and ascertain whether a different genetic background would support the three disease sites as independent entities.
  
  
  METHODS
  A panel of 29 SNPs of 19 IBD loci were analyzed by TaqMan SNP allelic discrimination method both evaluating their distinct contribute and analyzing all markers jointly.
  
  
  RESULTS
  Seven hundred and eight CD patients and 537 healthy controls were included in the study. Of the overall population of patients, 237 patients had an ileal involvement (L1), 171 a colonic localization (L2), and the 300 remaining an ileocolon location (L3). We confirmed the association for 23 of 29 variations (P < 0.05). Compared to healthy controls, 16 variations emerged as associated to an ileum disease, 7 with a colonic disease and 14 with an ileocolonic site (P < 0.05). Comparing ileum to colonic CD, 5 SNPs (17%) were differentially associated (P < 0.05). A genetic model score that aggregated the risks of 23 SNPs and their odds ratios (ORs), yielded an Area Under the Curve (AUC) of 0.70 for the overall CD patients. By analyzing each CD location, the AUC remained at the same level for the ileal and ileocolonic sites (0.73 and 0.72, respectively), but dropped to a 0,66 value in patients with colon localization.
  
  
  CONCLUSIONS
  Our findings reaffirm the existence of at least three different subgroups of CD patients, with a genetic signature distinctive for the three main CD sites.
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Orazio
authors.identifier: http://orcid.org/0000-0002-0019-7929
authors.initials: O
authors.lastname: Palmieri
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bossa
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Valvano
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corritore
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Latiano
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Martino
authors.affiliation: Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: D'Incà
authors.affiliation: Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
authors.affiliation: Division of Pediatrics, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pastore
authors.affiliation: Division of Pediatrics, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: D'Altilia
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Scimeca
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biscaglia
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
authors.affiliation: Division of Gastroenterology, "Casa Sollievo della Sofferenza" Hospital, IRCCS, San Giovanni Rotondo (FG), Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Latiano
mesh_terms: D000293:Adolescent; D000328:Adult; D003424:Crohn Disease / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007082:Ileum / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012372:ROC Curve; D055815:Young Adult
chemical_list: D005819:Genetic Markers