OBJECTIVE: The identification of CARD15 as a susceptibility gene for Crohn's disease (CD) offers new possibilities for patient classification and risk assessment. The purpose of this study was to carry out a CARD15 sequence analysis in a large single-center IBD cohort and to investigate the impact of different genotypes on disease phenotypes. MATERIAL AND METHODS: A total of 445 unrelated patients with IBD (68.1% CD, 28.5% ulcerative colitis (UC), 3.4% indeterminate colitis (IC)) were included in the study. Clinical data were recorded by detailed questionnaire and analysis of the charts. CARD15 variants (R702W, G908R, 1007fs (frameshift)) were identified by DNA sequence analysis. RESULTS: CARD15 variants were found in 142 inflammatory bowel disease (IBD) patients (31.9%) including 120 CD patients (39.6%). In CD, the presence of two CARD15 variants was associated with ileal disease (p=0.008 versus wild-type (wt); OR 4.04; 95% CI 1.36-11.96) and a fibrostenotic phenotype (p=0.002 versus wt; OR 5.47; 95% CI 1.61-18.58). Subgroup analysis of 19 patients (4.3%) homozygous for the CARD15 variant 1007fs (3020ins C) revealed an association with onset of CD at an early age (p=0.014 versus wt), ileal involvement (p=0.001), and intestinal stenoses in all patients (p=0.001) frequently requiring surgery (73.7%; p=0.093). Of these patients 78.6% developed re-stenoses after surgical resection; 52.6% of the homozygotes were diagnosed as having entero-enteral fistulas. CONCLUSIONS: Patients homozygous for the 1007fs mutation had an early disease onset with long-segment ileal stenoses and entero-enteral fistulas. They frequently needed surgical intervention and had a high risk of re-stenosis. Genotyping therefore appears to be an important diagnostic tool in identifying severely affected patients requiring individualized treatment strategies at an early stage of the disease.
OBJECTIVE: The identification of CARD15 as a susceptibility gene for Crohn's disease (CD) offers new possibilities for patient classification and risk assessment. The purpose of this study was to carry out a CARD15 sequence analysis in a large single-center IBD cohort and to investigate the impact of different genotypes on disease phenotypes. MATERIAL AND METHODS: A total of 445 unrelated patients with IBD (68.1% CD, 28.5% ulcerative colitis (UC), 3.4% indeterminate colitis (IC)) were included in the study. Clinical data were recorded by detailed questionnaire and analysis of the charts. CARD15 variants (R702W, G908R, 1007fs (frameshift)) were identified by DNA sequence analysis. RESULTS:CARD15 variants were found in 142 inflammatory bowel disease (IBD) patients (31.9%) including 120 CD patients (39.6%). In CD, the presence of two CARD15 variants was associated with ileal disease (p=0.008 versus wild-type (wt); OR 4.04; 95% CI 1.36-11.96) and a fibrostenotic phenotype (p=0.002 versus wt; OR 5.47; 95% CI 1.61-18.58). Subgroup analysis of 19 patients (4.3%) homozygous for the CARD15 variant 1007fs (3020ins C) revealed an association with onset of CD at an early age (p=0.014 versus wt), ileal involvement (p=0.001), and intestinal stenoses in all patients (p=0.001) frequently requiring surgery (73.7%; p=0.093). Of these patients 78.6% developed re-stenoses after surgical resection; 52.6% of the homozygotes were diagnosed as having entero-enteral fistulas. CONCLUSIONS:Patients homozygous for the 1007fs mutation had an early disease onset with long-segment ileal stenoses and entero-enteral fistulas. They frequently needed surgical intervention and had a high risk of re-stenosis. Genotyping therefore appears to be an important diagnostic tool in identifying severely affected patients requiring individualized treatment strategies at an early stage of the disease.
Authors: Matthias Jürgens; Stephan Brand; Rüdiger P Laubender; Julia Seiderer; Jürgen Glas; Martin Wetzke; Johanna Wagner; Simone Pfennig; Cornelia Tillack; Florian Beigel; Maria Weidinger; Fabian Schnitzler; Martin E Kreis; Burkhard Göke; Peter Lohse; Karin Herrmann; Thomas Ochsenkühn Journal: J Gastroenterol Date: 2010-04-29 Impact factor: 7.527
Authors: Paulo Freire; Ricardo Cardoso; Pedro Figueiredo; Maria M Donato; Manuela Ferreira; Sofia Mendes; Ana Margarida Ferreira; Helena Vasconcelos; Francisco Portela; Carlos Sofia Journal: Int J Colorectal Dis Date: 2014-03-22 Impact factor: 2.571
Authors: Jürgen Glas; Julia Seiderer; Melinda Nagy; Christoph Fries; Florian Beigel; Maria Weidinger; Simone Pfennig; Wolfram Klein; Jörg T Epplen; Peter Lohse; Matthias Folwaczny; Burkhard Göke; Thomas Ochsenkühn; Julia Diegelmann; Bertram Müller-Myhsok; Darina Roeske; Stephan Brand Journal: PLoS One Date: 2010-04-29 Impact factor: 3.240
Authors: Martin Storr; Dominik Emmerdinger; Julia Diegelmann; Simone Pfennig; Thomas Ochsenkühn; Burkhard Göke; Peter Lohse; Stephan Brand Journal: PLoS One Date: 2010-02-26 Impact factor: 3.240