title: Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease.
abstract: BACKGROUND
  To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene-gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype-phenotype correlation.
  
  
  METHODS
  In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis <19 years of age, and 651 controls were analyzed for SNPs rs9858542 and rs3197999.
  
  
  RESULTS
  BSN and MST1 were significantly associated with either CD (P(rs9858542) 2.5 x 10(-7); P(rs3197999) 3.9 x 10(-7)), and UC (P(rs9858542) = 3.1 x 10(-4); P(rs3197999) = 8 x 10(-4)). Prevalence of these variants was significantly increased in both adult and early-onset IBD patients. After stepwise logistic regression, the 2 variants were associated in adult UC with distal colitis (P(rs9858542) = 0.013, odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.16-3.59; P(rs3197999) = 0.018, OR 1.9, 95% CI 1.2-3.3), while the rs3197999 variant was inversely associated with occurrence of extraintestinal manifestations in adult CD(P = 0.017, OR 0.6, 95% CI 0.4-0.9).
  
  
  CONCLUSIONS
  We confirmed the association of BSN and MST1 with IBD susceptibility, either in the adult or the early-onset cohorts. These variants appeared to influence either the distal location of the disease in the UC cohort and extraintestinal manifestations in CD patients.
authors.affiliation: Division of Gastroenterology & Endoscopy, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Latiano
authors.forename: Orazio
authors.initials: O
authors.lastname: Palmieri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Corritore
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Valvano
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bossa
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cucchiara
authors.forename: Massimo
authors.initials: M
authors.lastname: Castro
authors.forename: Gabriele
authors.initials: G
authors.lastname: Riegler
authors.forename: Domenica
authors.initials: D
authors.lastname: De Venuto
authors.forename: Renata
authors.initials: R
authors.lastname: D'Incà
authors.forename: Angelo
authors.initials: A
authors.lastname: Andriulli
authors.forename: Vito
authors.initials: V
authors.lastname: Annese
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics* / Q000473:pathology; D003424:Crohn Disease / Q000235:genetics* / Q000473:pathology; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics; D055815:Young Adult
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin; D019204:GTP-Binding Proteins; C513539:IRGM protein, human