Inflammatory Bowel Disease
Subject Category: Inflammatory Bowel Disease
Am J Gastroenterol 2009; 104:110–116; doi:10.1038/ajg.2008.3
Polymorphism of the IRGM Gene Might Predispose to Fistulizing Behavior in Crohn's Disease
A Latiano BSc, PhD1, O Palmieri BSc, PhD1, S Cucchiara2, M Castro3, R D'Incà MD4, G Guariso MD5, B Dallapiccola6, M R Valvano MSc1, T Latiano1, A Andriulli MD1 and V Annese MD1
- 1Units of Gastroenterology and Endoscopy, IRCCS, "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
- 2Pediatric Gastroenterology and Liver Unit, La Sapienza University of Rome, Rome, Italy
- 3Gastroenterology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
- 4Department of Surgical and Gastroenterological Sciences, University of Padua, Italy
- 5Unit of Pediatric, University Hospital, Padua, Italy
- 6CSS Hospital, CSS-Mendel Institute, Rome, Italy
Correspondence: V. Annese, MD, Struttura Complessa di Endoscopia Digestiva, Ospedale "Casa Sollievo della Sofferenza"—IRCCS, Viale Cappuccini, 1, 71013 San Giovanni Rotondo, Italy. E-mail: v.annese@operapadrepio.it
Received 3 April 2008; Accepted 2 August 2008.
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=2.510-3, respectively) and childhood-onset (P=410-4; P=810-3, respectively) CD cohorts. Similarly, the genotype frequencies remained significantly different for both variants (adult rs1000113, P=110-4; rs4958847, P=110-3; pediatric rs1000113, P=2.310-4; rs4958847, P=9.610-3). 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).
