Associations between Genetic Polymorphisms in IL-33, IL1R1 and Risk for Inflammatory Bowel Disease

Anna Latiano, Orazio Palmieri, Luca Pastorelli, Maurizio Vecchi, Theresa T. Pizarro, Fabrizio Bossa, Giuseppe Merla, Bartolomeo Augello, Tiziana Latiano, Giuseppe Corritore, Alessia Settesoldi, Maria Rosa Valvano, Renata D'Incà, Laura Stronati, Vito Annese, Angelo Andriulli

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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. © 2013 Latiano et al.
Original languageEnglish
Article numbere62144
Pages (from-to)-
JournalPLoS One
Volume8
Issue number4
DOIs
Publication statusPublished - 25 Apr 2013
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Latiano, A., Palmieri, O., Pastorelli, L., Vecchi, M., Pizarro, T. T., Bossa, F., Merla, G., Augello, B., Latiano, T., Corritore, G., Settesoldi, A., Valvano, M. R., D'Incà, R., Stronati, L., Annese, V., & Andriulli, A. (2013). Associations between Genetic Polymorphisms in IL-33, IL1R1 and Risk for Inflammatory Bowel Disease. PLoS One, 8(4), -. [e62144]. https://doi.org/10.1371/journal.pone.0062144