Polymorphism of the IRGM Gene Might Predispose to Fistulizing Behavior in Crohn's Disease.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Subject Terms:
    • Abstract:
      OBJECTIVES: Recently, genome-wide association analyses have identified single nucleotide polymorphisms in the IRGM gene (rs1000113 and rs4958847) as strong candidate susceptibility factors for Crohn's disease (CD). The aim of our study was to test whether these variants are associated with inflammatory bowel disease (IBD) in adult- and childhood-onset Italian patients. METHODS: Allele and genotype frequencies of rs1000113 and rs4958847 were determined in 823 CD (265 younger than 19 years at diagnosis), 353 ulcerative colitis (UC) (130 younger than 19 years at diagnosis), and 578 controls. Genotype distributions were examined both within IBD clinical sub-phenotypes and CARD15 genotypes. RESULTS: rs1000113 and rs4958847 were both associated with adult-onset (P=2×10-4 ; P=2.5×10-3, respectively) and childhood-onset (P=4×10-4; P=8×10-3, respectively) CD cohorts. Similarly, the genotype frequencies remained significantly different for both variants (adult rs1000113, P=1×10-4; rs4958847, P=1×10-3; pediatric rs1000113, P=2.3×10-4; rs4958847, P=9.6×10-3). At logistic regression, the rs4958847 polymorphism was associated with fistulizing behavior (P=0.037, OR = 1.54, CI = 1.02-2.31) and perianal fistulas (P=0.045, OR = 1.55, CI = 1.01-2.38). Conversely, no association with UC and sub-phenotypes was shown. CONCLUSIONS: We replicated the previously reported associations between CD and rs1000113 and rs4958847, confirming that IRGM is a susceptibility locus only for CD, either adult- or early-onset in the Italian population; furthermore, we have also shown its influence on specific clinical features (fistulizing disease). [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of American Journal of Gastroenterology (Springer Nature) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)