Clinical and molecular characteristics of isolated colonic Crohn's disease

Laura Hancock, John Becky, Alessandra Geremia, Rachel Cooney, Fraser Cummings, Saad Pathan, Changun Guo, Bryan F. Warren, Neil Mortensen, Tariq Ahmad, Derek Jewell

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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 HLADRB1* 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.

Original languageEnglish
Pages (from-to)1667-1677
Number of pages11
JournalInflammatory Bowel Diseases
Volume14
Issue number12
DOIs
Publication statusPublished - 2008
Externally publishedYes

Fingerprint

Colonic Diseases
Crohn Disease
Odds Ratio
Confidence Intervals
Disease Susceptibility
Natural History
Alleles
Enema
Colon
Epidemiology
Databases
Inflammation
Polymerase Chain Reaction

Keywords

  • Colon
  • Crohn's disease
  • Genetics
  • Inflammatory bowel disease
  • Surgery

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Hancock, L., Becky, J., Geremia, A., Cooney, R., Cummings, F., Pathan, S., ... Jewell, D. (2008). Clinical and molecular characteristics of isolated colonic Crohn's disease. Inflammatory Bowel Diseases, 14(12), 1667-1677. https://doi.org/10.1002/ibd.20517

Clinical and molecular characteristics of isolated colonic Crohn's disease. / Hancock, Laura; Becky, John; Geremia, Alessandra; Cooney, Rachel; Cummings, Fraser; Pathan, Saad; Guo, Changun; Warren, Bryan F.; Mortensen, Neil; Ahmad, Tariq; Jewell, Derek.

In: Inflammatory Bowel Diseases, Vol. 14, No. 12, 2008, p. 1667-1677.

Research output: Contribution to journalArticle

Hancock, L, Becky, J, Geremia, A, Cooney, R, Cummings, F, Pathan, S, Guo, C, Warren, BF, Mortensen, N, Ahmad, T & Jewell, D 2008, 'Clinical and molecular characteristics of isolated colonic Crohn's disease', Inflammatory Bowel Diseases, vol. 14, no. 12, pp. 1667-1677. https://doi.org/10.1002/ibd.20517
Hancock L, Becky J, Geremia A, Cooney R, Cummings F, Pathan S et al. Clinical and molecular characteristics of isolated colonic Crohn's disease. Inflammatory Bowel Diseases. 2008;14(12):1667-1677. https://doi.org/10.1002/ibd.20517
Hancock, Laura ; Becky, John ; Geremia, Alessandra ; Cooney, Rachel ; Cummings, Fraser ; Pathan, Saad ; Guo, Changun ; Warren, Bryan F. ; Mortensen, Neil ; Ahmad, Tariq ; Jewell, Derek. / Clinical and molecular characteristics of isolated colonic Crohn's disease. In: Inflammatory Bowel Diseases. 2008 ; Vol. 14, No. 12. pp. 1667-1677.
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AU - Becky, John

AU - Geremia, Alessandra

AU - Cooney, Rachel

AU - Cummings, Fraser

AU - Pathan, Saad

AU - Guo, Changun

AU - Warren, Bryan F.

AU - Mortensen, Neil

AU - Ahmad, Tariq

AU - Jewell, Derek

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N2 - 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 HLADRB1* 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.

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