Open AccessClinical and molecular characteristics of isolated colonic Crohn's disease
Author(s) -
Hancock Laura,
Beckly John,
Geremia Alessandra,
Cooney Rachel,
Cummings Fraser,
Pathan Saad,
Guo Changun,
Warren Bryan F.,
Mortensen Neil,
Ahmad Tariq,
Jewell Derek
Publication year - 2008
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1002/ibd.20517
Subject(s) - medicine , gastroenterology , odds ratio , crohn's disease , disease , inflammatory bowel disease , confidence interval , epidemiology , cohort , colectomy , ulcerative colitis
Background: Clinical, serological, and molecular data support the existence of discrete subsets of Crohn's disease (CD) defined by location of disease. Little is known about the epidemiology and natural history of isolated CD of the colon (Montreal Classification L2) because most studies have not accurately distinguished it from ileocolonic disease. Our objectives were to describe the clinical features and natural history of isolated colonic CD in a rigorously characterized patient cohort and to investigate the association of polymorphisms in a number of genes with colonic location of disease and disease behavior. Methods: Patients with L2 disease were identified from a database of 675 CD patients. Only patients with a normal small bowel enema (70%), ileoscopy alone (30%), or both (20%) were included. Genotyping was performed using PCR‐SSP or the iPLEX platform. Results: In all, 135 patients were classified with L2 disease. L2 disease was more common in women (74.0% versus 58.0%; P = 0.0004; odds ratio [OR] = 2.11, 95% confidence interval [CI] 1.36–3.26) and in never smokers (48.9% versus 36.9%; P = 0.008; OR = 1.64, 95% CI 1.09–2.45); 20.7% underwent colonic resection for severe disease. We confirmed that carriage of the HLA‐DRB1*0103 allele is strongly associated with isolated colonic CD (14.9% versus 4.0%; P = 0.000016; OR 4.6, 95% CI 2.25–9.47) and report the novel association of this allele with time to first surgical event (log rank P = 0.001). There was no association with any of the known CD susceptibility loci ( NOD2 , IBD5 , NOD1 , IL23R , ATG16L1 ) and isolated colonic CD. A nonsynonymous polymorphism in MEKK1 (rs832582) was associated with CD susceptibility overall (15% versus 19%; P = 0.0083; OR = 1.28, 95% CI 1.07–1.54). The association was strongest in those patients not carrying a NOD2 mutation and had no effect on disease location. Conclusions: This study describes the clinical features of isolated colonic CD and demonstrates the importance of the HLA region in determining the molecular basis of colonic inflammation. (Inflamm Bowel Dis 2008)