Clinical and molecular characteristics of isolated colonic Crohn's disease
Corresponding Author
Laura Hancock MRCS
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UKSearch for more papers by this authorJohn Beckly MRCP
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorAlessandra Geremia MD
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorRachel Cooney MRCP
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorFraser Cummings MRCP
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorSaad Pathan DPhil
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorChangun Guo MD
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorBryan F. Warren FRCPath
Department of Cellular Pathology, John Radcliffe Hospital, Oxford, UK
Search for more papers by this authorNeil Mortensen MD, FRCS
Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, UK
Search for more papers by this authorTariq Ahmad DPhil
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorDerek Jewell DPhil
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorCorresponding Author
Laura Hancock MRCS
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UKSearch for more papers by this authorJohn Beckly MRCP
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorAlessandra Geremia MD
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorRachel Cooney MRCP
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorFraser Cummings MRCP
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorSaad Pathan DPhil
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorChangun Guo MD
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorBryan F. Warren FRCPath
Department of Cellular Pathology, John Radcliffe Hospital, Oxford, UK
Search for more papers by this authorNeil Mortensen MD, FRCS
Department of Colorectal Surgery, John Radcliffe Hospital, Oxford, UK
Search for more papers by this authorTariq Ahmad DPhil
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorDerek Jewell DPhil
Gastroenterology Unit, Gibson Laboratories, Radcliffe Infirmary, Oxford, UK
Search for more papers by this authorAbstract
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)
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