S110 Conclusions: In terms of age at onset and gender Polish data appear similar to other European countries. The predominant disease location is terminal ileum. Almost half of patients had undergone at least one surgical intervention. P250 Autophagy 16-like 1 on chromosome 2q37.1 is associated with inflammatory bowel disease in children A. Jurik1 *, M. Lacher1 , S. Schr¨ opf1 , R. Kappler1 , D. von Schweinitz1 , S. Koletzko2 . 1 Pediatric Surgical Clinic, Research Laboratories, University of Munich, Munich, Germany, 2 Pediatric Clinic, Gastroenterology, University of Munich, Munich, Germany Introduction: Genome-wide association studies have described a variety of susceptibility genes for IBD. Among them, a polymorphism within the autophagy 16-like gene ATG16L1 has been shown to be associated with Crohn’s disease in independent IBD cohorts. In this gene, which encodes a small coiled-coil domain protein that is part of a protein complex essential for autophagy, the rs2241880 variant leads to a threonine-to-alanine substitution at amino acid position 300 (T300A) and confers strong risk for CD in adults. This locus has been evaluated in three pediatric IBD cohorts with conflicting results. Therefore, the aim of this study was to investigate the association of rs2241880 in a German pediatric IBD cohort and to describe the transcriptional activity of ATG16L1 in colonic tissues. Methods: Subjects: 232 German Caucasian children with IBD (152 CD, 80 UC) and 253 ethnically matched healthy adult blood donors. Gene expression analysis: Determination of mRNA expression of ATG16L1 and IL-8 as a proinflammatory control in large bowel biopsies of selected IBD patients and controls using real-time PCR. Genotyping: Investigation of the rs2241880 polymorphism of the ATG16L1 gene on chromosome 2q37.1 using a pre-designed TaqMan® SNP Genotyping Assay (Applied Biosystems, Foster City, CA, USA). To verify potential interactions of the T300A variant with the NOD2/CARD15 gene we also tested for epistasis with NOD2/CARD15. Results: Genotyping for the rs2241880 polymorphism exhibited significant differences in the genotypes between CD patients and controls (p < 0.01), whereas there were no differences between UC patients and controls in genotype or allele frequencies. Subgrouping for phenotypes according to disease localization and behavior showed no significant differences in the frequency of the genotypes. We could not demonstrate an epistatic interaction between the NOD2/CARD15 gene and the A300T variant of the ATG16L1 gene. The gene expression analysis did not reveal a characteristical overexpression or downregulation of ATG16L1 in CD and UC patients compared to unaffected controls. Conclusion: We have confirmed the association between CD and the rs2241880 polymorphism in ATG16L1 in a pediatric cohort of German Caucasian children. However, no association of UC and A300T variant could be found. We could not demonstrate an epistatic interaction between the NOD2/CARD15 gene and the rs2241880 polymorphism. These results mirror the findings in adult patients that even in the absence of NOD2/CARD15 mutations the ATG16L1 variation is a risk factor in pediatric CD thereby supporting a role for autophagy in the pathogenesis of this disease.
Poster Presentations P251 Clinical parameters available in early Crohn’s disease patients predict a progressive disease course and the subsequent need for immunosuppressive therapy S. Wenger1 *, S. Nikolaus2 , S. Howaldt3 , B. Bokemeyer4 , A. Sturm5 , J. Preiß6 , A. Stallmach1 , C. Schmidt1 . 1 FriedrichSchiller-University, Clinic of Internal Medicine II, Jena, Germany, 2 Christian Albrechts-University, Clinic of Internal Medicine, Kiel, Germany, 3 Gastroenterologie am Rothenbaum, Hamburg, Germany, 4 Gastroenterologische Gemeinschaftspraxis, Minden, Germany, 5 Charite, Campus Virchow Clinic, Clinic of Internal Medicine, Berlin, Germany, 6 Charite, Campus Benjamin Franklin, Medical Clinic I, Berlin, Germany Aim: The clinical course of Crohn’s disease (CD) is highly variable and ranges from a single episode to a potentially life-threatening continuous disease. However, reliable clinical parameters on an individual basis in order to identify patients at risk for a chronic disease course early in a patient’s case history have not been established so far. Materials and Methods: We performed a retrospective analysis of 437 CD patients from 5 german IBD centers. Patients’ data were investigated concerning clinical parameters available during an early phase after the initial diagnosis of CD in order to identify patients who subsequently will exhibit a severe course of the disease requiring immunosuppressive therapy. Results: In 300 patients (68.6%) the course of Crohn’s disease necessitated immunosuppressive therapy. Among these patients 95% received azathioprine, 7.7% methotrexate, 10.3% 6-mercaptopurine, 28.7% infliximab, 14% adalimumab and 1.7% certolizumab, resp. Side effects of this therapy have been reported by 20% of patients. Several clinical parameters were differentially prevalent in the two groups. Patients requiring immunosuppressors were younger at symptom onset (23.0 vs. 27.0 years) and at first diagnosis (25.0 vs. 30.0 years). Likewise, these patients showed a manifestation of the upper GI tract, ileocolonic disease and perianal manifestations as well as fever at the first presentation of CD more often. Most important, these patients required systemic steroid therapy at first diagnosis more often than patients without subsequent immunosuppressive treatment (66.7 vs. 39.3%) and, moreover, in these patients steroid therapy failed frequently. However, in our population smoking habits were not different between the two groups. Conclusion: Based on our large group of Crohn’s disease patients several clinical parameters that are both easy and early to obtain are able to predict a progressive course of the disease. The patients identified thus are very likely to benefit from an early immunosuppressive therapy that finally may change the natural course of Crohn’s disease. P252 Characteristics of patients prospectively recruited in the Hungarian Pediatric IBD Registry (HUPIR) G. Veres1 *, Hungarian Pediatric IBD Registry Group (HUPIR)1 , M. Papp2 , P. Lakatos3 . 1 1st Dept of Pediatrics, Budapest, Hungary, 2 2nd Department of Medicine, Debrecen, Hungary, 3 1st Dept of Medicine, Budapest, Hungary Background and Aims: On behalf of the of Hungarian Pediatric Gastroenterology Society prospective registry of pediatric inflammatory bowel disease (IBD) was launched from the 1st of January 2007 with the cooperation of 27 institutes (clinics, hospitals, outpatient departments) ensuring the coverage of the whole country. The survey data has been forwarded online to the center of the European Pediatric IBD Registry (Rotterdam). In recent epidemiological studies from Europe and North America the reported incidence of childhood Crohn disease (CD) is 3 4 cases per 100.000 per year, and of ulcerative
Abstracts of the 4th Congress of ECCO
the European Crohn’s and Colitis Organisation
colitis (UC) 2 3 cases per 100.000 per year. So far the incidence of pediatric IBD in Hungary is unknown. Methods: The participating institutes are requested to fill out a questionnaire (78 parameters) about every newly diagnosed IBD patients younger than 18 years. The questionnaire is about epidemiological and antropometrical data, main symptoms, diagnostic procedures (endoscopy, CT, MRI), and the detailed results of histological and imaging procedures. Results: Between 01.01.2007 and 30.09.2008 223 newly diagnosed cases of IBD were prospectively identified: 139 cases of CD, 69 cases of UC and 15 cases of indeterminate colitis. As a result the incidence of childhood IBD was 6.13 cases per 100.000, with the incidence of CD being 4.07 cases per 100.000 per year, the incidence of UC 1.67 cases per 100.000 per year and the incidence of indeterminate colitis 0.40 cases per 100.000 per year. The mean age at diagnosis was 13 years (range: 1.5 18 year). There was a male preponderance in CD, in contrast, sex ratio in UC patients were equal. Positive family history of IBD was registered in 7.8% of patients and 9.2% of patients with CD were reported to have a fistula. Ileoscopy rate was only 48% technical problem was the most common reason for the lack of ileal intubation. Oesophagogastro-duodenoscopy was performed in 50% of all cases. In 35% were MRI or CT scan made for the detailed verification of the disease. Conclusions: The incidences reported in the first 21 months of HUPIR are similar to the European and North American data. The dominance of CD proved to be also consistent with other studies. Almost 10% of the patients with CD had fistula. Ileal intubation and oesophago-gastro-duodenoscopy were performed in the half of the cases, and this rate should be improved in the future. P253 The role of pregnane X receptor (PXR/NR1I2) gene variants in inflammatory bowel disease J. Seiderer1 *, J. Glas1 , J. Diegelmann1 , D. Fischer1 , B. Seitz1 , S. Pfennig1 , T. Griga2 , W. Klein3 , J.T. Epplen3 , U. Schiemann4 , T. Mussack5 , B. G¨ oke1 , T. Ochsenk¨ uhn1 , M. Folwaczny6 , B. M¨ uller-Myhsok7 , S. Brand1 . 1 University of Munich Klinikum Großhadern, Munich, Germany, 2 Department of Internal Medicine, Knappschaftskrankenhaus Dortmund, Dortmund, Germany, 3 Department of Human Genetics, Ruhr-University, Bochum, Bochum, Germany, 4 Department of General Internal Medicine, Inselspital Bern, Bern, Switzerland, 5 University of Munich Department of Surgery, Munich, Germany, 6 Clinic for Preventive Dentistry and Parodontology, LMU Munich, Munich, Germany, 7 Biostatistics, Max-Planck-Institute for Psychiatry, Munich-Schwabing, Munich, Germany Introduction: The pregnane X receptor (PXR), also known as NR1I2 (nuclear receptor subfamily 1, group I, member 2), is a nuclear receptor encoded by the PXR/NR1I2 gene. The PXR/NR1I2 gene has recently been reported to be associated with susceptibility to inflammatory bowel disease (IBD) (Gastroenterology 2006;130:341 8). However, since a subsequent case-control study failed to replicate this association in an independent population, further replication studies in different ethnic cohorts are required. We therefore investigated this potential association in a large European IBD cohort. Aims and Methods: Genomic DNA from 2823 Caucasian individuals including 859 patients with Crohn’s disease (CD), 464 patients with ulcerative colitis (UC), and 1500 healthy unrelated controls was analyzed for eight single nucleotide polymorphisms (SNPs) in the pregnane X receptor (PXR/NR1I2) gene (rs12721602, rs3814055, rs1523128, rs1523127, rs12721607, rs6785049, rs2276707, rs3814057). Genotyping was performed by PCR and melting curve analysis
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using a pair of fluorescence resonance energy transfer (FRET) probes in a Light Cycler. Results: With the exception of a weak association of rs2276707 with UC (p = 1.02 x 10 2; OR 1.27 [1.06 1.52]), none of the analyzed variants in the pregnane X receptor (PXR/NR1I2) was associated with susceptibility to CD or to UC in our study population. Conclusion: Our data could not confirm the association of PXR gene variants with CD or UC. Further studies investigating the phenotypic effect and potential epistatic interactions of PXR with other IBD susceptibility genes are required to determine the exact role of PXR in IBD. P254 Incidence of nonspecific ulcerative colitis in Republic of Tatarstan (first Russian inflammatory bowel diseases registry) R.A. Abdulkhakov, S.R. Abdulkhakov *, A.A. Abbakumova. Kazan State Medical University, Kazan, Russian Federation The purpose of the study was to find out the real incidence of nonspecific ulcerative colitis (NUC) in Republic of Tatarstan. Materials and Methods: The registry of NUC patients was made according to case histories and out-patient charts including those who presented with the first onset of the disease as well as those with relapses or stable remission. Results: According to the registry there are 428 NUC patients in Republic of Tatarstan (m-216, 50.47%, f-212, 49.53%, NS). Incidence of NUC is 11.4 per 100000 of population. Acute NUC was revealed in 13 (3%) patients, chronic persistent NUC in 38 (8.9%) patients. Most of the patients (277 pts, 64.7%) had chronic relapsing type of disease which was observed quite often both in males (138 pts) and females (139 pts). In case of 76 patients it was first admission to the hospital due to complaints associated with NUC. In most of patients (150 pts, 35%) distal colitis was observed, in 89 (21%) total colitis, in 32 (7.5%) subtotal, left-sided colitis was found in 125 (29.2%) patients, in case of 32 patients there were no data about the localization of inflammation. According to severity of inflammation distribution of patients was the following: mild inflammation was found in 70 (16.4%) cases, moderate in 237 (55.4%), severe in 61 (14.3%) patient, in case of 60 patient data was lacking. Massive bleeding as a complication of NUC occurred in 10 (2.3%) patients, 4 of them underwent surgery. NUC was the cause of disability in 79 (18.5%) patients. Conclusions: It’s the first registry of NUC patients in Republic of Tatarstan which covered 428 NUC patients and revealed incidence of NUC as 11.4 per 100000 of population. NUC incidence is the same in men and women. Most of patients have distal type of NUC with moderate activity. Frequency of massive bleeding as NUC complication is 2.3%. P255 Anxiety and depression symptoms in Crohn’s disease patients in remission M. Iglesias1 , M. Barreiro2 *, A. Figueiras3 , M. Vazquez4 , L. Nieto1 , M. Seoane2 , A. Lorenzo2 , J.E. Dominguez-Mu˜ noz2 . 1 FIENAD University Hospital, Santiago de Compostela, Spain, 2 Gastroenterology University Hospital, Santiago de Compostela, Spain, 3 Epidemiology University Hospital, Santiago de Compostela, Spain, 4 Clinic Psycology University of Santiago, Santiago de Compostela, Spain Background: Crohn’s disease (CD) is a chronic inflammatory bowel disease with periods of relapse and remission. Role of anxiety and depression in CD patients in remission has been poorly studied. We hypothesized that despite staying in remission, anxiety and depression symptoms have an import role in CD patients. Aim of the study was to evaluate the presence of anxiety and depression symptoms in CD patients in remission and potential