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P139 GENETIC ASSOCIATION OF CARD15 VARIANTS WITH CROHN'S DISEASE IN THE CZECH POPULATION
Abstracts of ECCO Congress, Innsbruck, Austria, 1—3 March 2007 P136 CONTRIBUTION OF GENETIC AND ENVIRONMENTAL FACTORS IN THE PATHOGENESIS OF CROHN' S DISEASE IN A LARGE FAMILY WITH MULTIPLE CASES M. Joossens 1 , M. Simoens 2 , S. Vermeire 1 , X. Bossuyt 3 , K. Geboes 4 , P. Rutgeerts 1 . 1 Department of Gastroenterology, University Hospital Leuven, Belgium; 2 Department of Gastroenterology, Jan Palfijn Hospital, Antwerp, Belgium; 3 Laboratory Medicine, University Hospital Leuven, Belgium; 4 Department of Pathology, University Hospital Leuven, Belgium Background: A large family of Moroccan immigrants was investigated. In this family the father developed Crohn' s disease after moving from Morocco to Belgium and successively 4 of his 8 children subsequently developed Crohn' s disease. There was no previous history of familial Crohn' s disease. Methods: The family was interviewed at their home and an elaborated questionnaire was completed. The food and sanitation characteristics of the family were investigated. Moreover serological markers were tested in all family members including ASCA, gASCA, ALCA, ACCA, Omp and ANCA, using enzymelinked immunosorbent assay and indirect immunofluorescence. Genetic variants in CARD15, TLR4, NOD1, CARD8 and DLG5 associated with Crohn' s disease were tested as well. The complete medical history of all patients was reviewed. Results: There were no known genetic variants associated with Crohn' s disease in this family. None of the serological antibodies could discriminate between patients and unaffected family members although the antibody titers were higher in diseased family members as compared with the healthy family members. Conclusion: The occurrence of 5 new cases of Crohn' s disease within one Moroccan family after immigration to Belgium cannot be explained by the known genetic susceptibility factors, and thus suggests a major environmental factor probably not related to sanitation in childhood.
P137 COLECTOMIZE OR NOT IN ULCERATIVE COLITIS— THAT' S THE QUESTION T. Bernklev 1 , O. Høie 2 , C. Solberg 3 , M. Henriksen 4 , F. Wolters 5 , R. Stockbrügger 5 , E. Langholz 6 , P. Munkholm 7 , M. Vatn 8 , B. Moum 1 . 1 Aker University Hospital, Oslo, Norway; 2 Sørlandet Hospital, Arendal, Norway; 3 Ullevål University Hospital, Oslo, Norway; 4 Østfold Hospital, Fredrikstad, Norway; 5 Maastricht University Hospital, The Netherlands; 6 Gentofte Hospital, Copenhagen, Denmark; 7 Herlev University Hospital, Copenhagen, Denmark; 8 EPIGEN, Akershus University Hospital, Oslo, Norway Background: We have previously shown that health-related quality of life (HRQOL) in patients with ulcerative colitis (UC) seems to differ throughout Europe, as well as colectomy rates. Aim: To determine if differences in colectomy rates affect the HRQOL in UC patients from Maastrich (the Netherlands), Copenhagen (Denmark) and Oslo (Norway), all part of the EC-IBD cohort. Material and Methods: The EC-IBD cohort of patients has prospectively been followed since 1990. In 2004, patients were invited to a 10-year follow-up visit, where demographic and clinical data were obtained. All patients also completed a generic HRQOL questionnaire, the SF-36. In addition, colectomy rates and cost figures were obtained. In total, 426 UC patients from the three centres were included, mean age 46.6 years, 48% females. Results: The colectomy rates in this subgroup of patients were 25,8% (Copenhagen), 9,5% (Maastricht) and 7% (Oslo). In Copenhagen, colectomized UC patients had between 8%-20% reduction in HRQOL score compared to patients without a colectomy, particularly within the dimensions Physical Functioning, Role Physical, General Health and Vitality. In Norway, we found an increased HRQOL score in colectomized patients of 10%-15% in the dimensions Role Physical and Bodily Pain compared to patients without having a colectomy. The colectomized patients from Maastrich had a decreased score in the dimensions Physical Functioning (-14%) and Role Physical (-28%), and increased scores for the dimensions Vitality (+8%) and Social Functioning (+13%), compared to non-operated patients. Conclusion: HRQOL differences was observed between operated and nonoperated UC patients according to colectomy frequencies in these three IBD centres. These findings could indicate that some patients should have been colectomised in an earlier stage while others would benefit of prolonged but more potent medical therapy. This underscores the importance of developing more objective criteria in patients with relapsing disease for which patients to be colectomized.
39 P138 ARE THERE OTHER FACTORS EXPLAINING WHY UC-PATIENTS WITH NORMAL COLONOSCOPY STILL REPORT IBD-RELATED SYMPTOMS? T. Bernklev 1 , M. Henriksen 2, J. Jahnsen 1 , Ø. Palm 3 , M. Vatn 4 , B. Moum 1 . 1 Aker University Hospital, Oslo, Norway; 2 Østfold Hospital, Fredrikstad, Norway; 3 Rikshospitalet University Hospital, Oslo, Norway; 4 EPIGEN, Akershus University Hospital, Oslo, Norway Background: It is well known from clinical practice that IBD patients with inactive disease, judged by colonoscopy and histology, may well complain of disease-related symptoms. The lack of objective findings makes it difficult to explain this, but other, non-IBD related factors may contribute to their symptoms. Aim: To identify possible factors explaining the presence of symptoms in UC-patients with inactive disease at the time of investigation. Material and Method: All UC patients in the IBSEN cohort were offered a colonoscopy with biopsies in connection with the five-year follow-up visit. Disease symptoms were classified as none, mild, moderate/severe by the patient, judged on the last 14 days before the visit. Health-related quality of life was investigated with N-IBDQ and SF-36. All patients underwent a clinical examination and interview. In addition, the frequencies of fibromyalgia (FM), chronic widespread pain (CWP) and non-inflammatory joint pain (NIJP) were determined by an experienced rheumatologist. Results: All together 164 UC patients (50%) accepted and underwent a colonoscopy, mean age 45.3yrs (15.4), 47% female. Of these, 28 patients (17%) complained of IBD-related symptoms but had a normale colonoscopy; mean age 47.4(14.3), 46% female. HRQOL was significantly reduced for the dimensions stool consistency/frequency, bowel pain and worries, compared to UC patients without symptoms. Of all patients with FM/CWP in the IBSEN study, 25% were found in this subgroup, compared to 2.7% in symptom-free UC patients. Smoking was also more frequent in this subgroup, as well as a lower educational level, compared to symptom-free UC patients,18% vs. 8% and 36% vs. 24%, respectively. Conclusion: UC patients with normal colonoscopy and symptoms are more frequently smokers, have a lower education, have an increased risk for having FM/CWP and have more bowel complains, bowel pain and worries than symptom-free UC patients.
P139 GENETIC ASSOCIATION OF CARD15 VARIANTS WITH CROHN' S DISEASE IN THE CZECH POPULATION M. Lenicek 1 , O. Hradsky 2 , O. Cinek 2 , M. Lukas 3 , J. Bronsky 2 , M. Bortlik 3 , R. Donoval 3 , L. Vitek 1 . 1 Department of Clinical Biochemistry and Laboratory Diagnostics, Charles University, Prague, Czech Republic; 2 Department of Pediatrics, University Hospital Motol, Prague, Czech Republic; 3 4th Department of Internal Medicine, General Faculty Hospital, Prague, Czech Republic Background and Aims: Three polymorphisms in the CARD15 gene have been repeatedly shown to be associated with Crohn' s disease (CD). However, data from central and eastern part of Europe are scarce. The aim of our study was therefore to analyze the association in the Czech population. Methods: Genotype, phenotype and allelic frequencies were compared between 293 patients with CD (113 with childhood-onset, and 180 with adultonset disease) and 389 control subjects. The genotypes of the 1007fs, R702W, and G908R polymorphisms were determined using TaqMan SNP assays or by PCR-RFLP. Association was first assessed in univariate analyses, and then in a multiple logistic regression model. Results: At least one minor allele was carried by 49% patients and 33% controls; each dose of minor allele increased the risk 2.8-fold (95%CI 2.0- 3.8). In a multiple model, the phenotypic positivity for minor alleles of the three polymorphisms increased the CD risk in an independent manner. The 1007fs was associated with OR=3.7 (95%CI 2.4 - 5.8), R702W with OR=1.8 (95%CI 1.0 - 3.0), G908R with OR=2.7 (95%CI 1.3 - 5.8). No significant differences were detected between the pediatric-onset and adult-onset CD subgroups. Conclusion: We observed a strong association between CD and the 1007fs polymorphisms, with a moderate independent contribution of the other two variants. Acknowledgement: Supported by the Czech Ministry of Education, grant 226008 and by the Czech Ministry of Health, grant 00064203.
P137 COLECTOMIZE OR NOT IN ULCERATIVE COLITIS— THAT' S THE QUESTION T. Bernklev 1 , O. Høie 2 , C. Solberg 3 , M. Henriksen 4 , F. Wolters 5 , R. Stockbrügger 5 , E. Langholz 6 , P. Munkholm 7 , M. Vatn 8 , B. Moum 1 . 1 Aker University Hospital, Oslo, Norway; 2 Sørlandet Hospital, Arendal, Norway; 3 Ullevål University Hospital, Oslo, Norway; 4 Østfold Hospital, Fredrikstad, Norway; 5 Maastricht University Hospital, The Netherlands; 6 Gentofte Hospital, Copenhagen, Denmark; 7 Herlev University Hospital, Copenhagen, Denmark; 8 EPIGEN, Akershus University Hospital, Oslo, Norway Background: We have previously shown that health-related quality of life (HRQOL) in patients with ulcerative colitis (UC) seems to differ throughout Europe, as well as colectomy rates. Aim: To determine if differences in colectomy rates affect the HRQOL in UC patients from Maastrich (the Netherlands), Copenhagen (Denmark) and Oslo (Norway), all part of the EC-IBD cohort. Material and Methods: The EC-IBD cohort of patients has prospectively been followed since 1990. In 2004, patients were invited to a 10-year follow-up visit, where demographic and clinical data were obtained. All patients also completed a generic HRQOL questionnaire, the SF-36. In addition, colectomy rates and cost figures were obtained. In total, 426 UC patients from the three centres were included, mean age 46.6 years, 48% females. Results: The colectomy rates in this subgroup of patients were 25,8% (Copenhagen), 9,5% (Maastricht) and 7% (Oslo). In Copenhagen, colectomized UC patients had between 8%-20% reduction in HRQOL score compared to patients without a colectomy, particularly within the dimensions Physical Functioning, Role Physical, General Health and Vitality. In Norway, we found an increased HRQOL score in colectomized patients of 10%-15% in the dimensions Role Physical and Bodily Pain compared to patients without having a colectomy. The colectomized patients from Maastrich had a decreased score in the dimensions Physical Functioning (-14%) and Role Physical (-28%), and increased scores for the dimensions Vitality (+8%) and Social Functioning (+13%), compared to non-operated patients. Conclusion: HRQOL differences was observed between operated and nonoperated UC patients according to colectomy frequencies in these three IBD centres. These findings could indicate that some patients should have been colectomised in an earlier stage while others would benefit of prolonged but more potent medical therapy. This underscores the importance of developing more objective criteria in patients with relapsing disease for which patients to be colectomized.
39 P138 ARE THERE OTHER FACTORS EXPLAINING WHY UC-PATIENTS WITH NORMAL COLONOSCOPY STILL REPORT IBD-RELATED SYMPTOMS? T. Bernklev 1 , M. Henriksen 2, J. Jahnsen 1 , Ø. Palm 3 , M. Vatn 4 , B. Moum 1 . 1 Aker University Hospital, Oslo, Norway; 2 Østfold Hospital, Fredrikstad, Norway; 3 Rikshospitalet University Hospital, Oslo, Norway; 4 EPIGEN, Akershus University Hospital, Oslo, Norway Background: It is well known from clinical practice that IBD patients with inactive disease, judged by colonoscopy and histology, may well complain of disease-related symptoms. The lack of objective findings makes it difficult to explain this, but other, non-IBD related factors may contribute to their symptoms. Aim: To identify possible factors explaining the presence of symptoms in UC-patients with inactive disease at the time of investigation. Material and Method: All UC patients in the IBSEN cohort were offered a colonoscopy with biopsies in connection with the five-year follow-up visit. Disease symptoms were classified as none, mild, moderate/severe by the patient, judged on the last 14 days before the visit. Health-related quality of life was investigated with N-IBDQ and SF-36. All patients underwent a clinical examination and interview. In addition, the frequencies of fibromyalgia (FM), chronic widespread pain (CWP) and non-inflammatory joint pain (NIJP) were determined by an experienced rheumatologist. Results: All together 164 UC patients (50%) accepted and underwent a colonoscopy, mean age 45.3yrs (15.4), 47% female. Of these, 28 patients (17%) complained of IBD-related symptoms but had a normale colonoscopy; mean age 47.4(14.3), 46% female. HRQOL was significantly reduced for the dimensions stool consistency/frequency, bowel pain and worries, compared to UC patients without symptoms. Of all patients with FM/CWP in the IBSEN study, 25% were found in this subgroup, compared to 2.7% in symptom-free UC patients. Smoking was also more frequent in this subgroup, as well as a lower educational level, compared to symptom-free UC patients,18% vs. 8% and 36% vs. 24%, respectively. Conclusion: UC patients with normal colonoscopy and symptoms are more frequently smokers, have a lower education, have an increased risk for having FM/CWP and have more bowel complains, bowel pain and worries than symptom-free UC patients.
P139 GENETIC ASSOCIATION OF CARD15 VARIANTS WITH CROHN' S DISEASE IN THE CZECH POPULATION M. Lenicek 1 , O. Hradsky 2 , O. Cinek 2 , M. Lukas 3 , J. Bronsky 2 , M. Bortlik 3 , R. Donoval 3 , L. Vitek 1 . 1 Department of Clinical Biochemistry and Laboratory Diagnostics, Charles University, Prague, Czech Republic; 2 Department of Pediatrics, University Hospital Motol, Prague, Czech Republic; 3 4th Department of Internal Medicine, General Faculty Hospital, Prague, Czech Republic Background and Aims: Three polymorphisms in the CARD15 gene have been repeatedly shown to be associated with Crohn' s disease (CD). However, data from central and eastern part of Europe are scarce. The aim of our study was therefore to analyze the association in the Czech population. Methods: Genotype, phenotype and allelic frequencies were compared between 293 patients with CD (113 with childhood-onset, and 180 with adultonset disease) and 389 control subjects. The genotypes of the 1007fs, R702W, and G908R polymorphisms were determined using TaqMan SNP assays or by PCR-RFLP. Association was first assessed in univariate analyses, and then in a multiple logistic regression model. Results: At least one minor allele was carried by 49% patients and 33% controls; each dose of minor allele increased the risk 2.8-fold (95%CI 2.0- 3.8). In a multiple model, the phenotypic positivity for minor alleles of the three polymorphisms increased the CD risk in an independent manner. The 1007fs was associated with OR=3.7 (95%CI 2.4 - 5.8), R702W with OR=1.8 (95%CI 1.0 - 3.0), G908R with OR=2.7 (95%CI 1.3 - 5.8). No significant differences were detected between the pediatric-onset and adult-onset CD subgroups. Conclusion: We observed a strong association between CD and the 1007fs polymorphisms, with a moderate independent contribution of the other two variants. Acknowledgement: Supported by the Czech Ministry of Education, grant 226008 and by the Czech Ministry of Health, grant 00064203.