title: Associations between genetic polymorphisms in IL-33, IL1R1 and risk for inflammatory bowel disease.
abstract: BACKGROUND
  Recent evidence suggests that the IL-33/IL1RL1 axis plays a critical role in several autoimmune and inflammatory disorders; however, its mechanistic role in inflammatory bowel disease (IBD) has not been clearly defined. We investigated the contribution of IL-33 and IL1RL1 polymorphisms to IBD risk, and possible correlations with phenotype in an Italian cohort of adult and pediatric patients.
  
  
  METHODS
  We evaluated the association of six SNPs in IL-33 and IL1RL1 genes, in 805 Crohn's disease (CD), 816 ulcerative colitis (UC), and 752 controls, using Taqman. IL-33 and IL1RL1 mRNA expression was also analyzed.
  
  
  RESULTS
  Significant allele and genotype associations with IL-33 rs3939286 were found in CD (P = 0.004; P = 0.035) and UC patients (P = 0.002; P = 0.038). After stratifying the cohort for age at diagnosis, the differences remained significant only in the IBD adult-onset. Significant associations were also obtained in CD patients with two IL1RL1 polymorphisms (rs13015714 and rs2058660, P<0.015). By combining homo- and heterozygous carriers of the rs13015714 risk allele, differences were still significant for both CD adult- and pediatric-onset. Upon genotype-phenotype evaluation, an increased frequency of extensive colitis in adult UC (P = 0.019) and in steroid-responsive pediatric patients (P = 0.024) carrying the IL-33 rs3939286 risk genotype, was observed. mRNA expression of IL-33 and IL1RL1 in inflamed IBD biopsy samples was significantly increased.
  
  
  CONCLUSIONS
  Common IL-33 and IL1RL1 polymorphisms contribute to the risk of IBD in an Italian cohort of adult and pediatric patients, with some influence on sub-phenotypes.
authors: Division of Gastroenterology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. a.latiano@operapadrepio.it
authors: Anna
authors: A
authors: Latiano
authors: Orazio
authors: O
authors: Palmieri
authors: Luca
authors: L
authors: Pastorelli
authors: Maurizio
authors: M
authors: Vecchi
authors: Theresa T
authors: TT
authors: Pizarro
authors: Fabrizio
authors: F
authors: Bossa
authors: Giuseppe
authors: G
authors: Merla
authors: Bartolomeo
authors: B
authors: Augello
authors: Tiziana
authors: T
authors: Latiano
authors: Giuseppe
authors: G
authors: Corritore
authors: Alessia
authors: A
authors: Settesoldi
authors: Maria Rosa
authors: MR
authors: Valvano
authors: Renata
authors: R
authors: D'Incà
authors: Laura
authors: L
authors: Stronati
authors: Vito
authors: V
authors: Annese
authors: Angelo
authors: A
authors: Andriulli
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics*; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics*; D055815:Young Adult
chemical_list: C508590:IL1R1 protein, human; C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D053573:Receptors, Interleukin-1 Type I
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