المؤلفون: Beaudoin, Melissa, Goyette, Philippe, Goel, Gautam, Louis, E., Mansfield, J. C., Mathew, C. G., McGovern, D. P., Mitrovic, M., Montgomery, G. W., Mowat, C., Newman, W., Palmieri, O., Panés, J., Lagace, Caroline, Parkes, M., Phillips, A., Ponsioen, C. Y., Potocnik, U., Prescott, N. J., Proctor, D. D., Radford-Smith, G. L., Regueiro, M., Rioux, J. D., Roberts, R., Annese, Vito, Rotter, J. I., Rutgeerts, P., Sanderson, J., Sans, M., Satsangi, J., Schreiber, S., Schumm, P., Seibold, F., Sharma, Y., Silverberg, M. S., Bitton, Alain, Simms, L. A., Steinhart, A., Targan, S. R., Taylor, K. D., Torkvist, L., Vermeire, S., Halfvarson, J., Verspaget, H. W., De Vos, M., Walters, T., Begun, Jakob, Wang, K., Weersma, R. K., Whiteman, D., Wijmenga, C., Brant, Steven R., Bresso, Francesca, Cho, Judy H., Duerr, Richard H., Halfvarson, Jonas, Boucher, Gabrielle, McGovern, Dermot P. B., Radford-Smith, Graham, Schreiber, Stefan, Schumm, Philip L., Sharma, Yashoda, Silverberg, Mark S., Weersma, Rinse K., Quebec IBD Genetics Consortium, NIDDK IBD Genetics Consortium, International IBD Genetics Consortium (IIBDGC), Lo, Ken Sin, D'Amato, Mauro, Vermeire, Severine, Franke, Andre, Lettre, Guillaume, Xavier, Ramnik J., Daly, Mark J., Rioux, John D., Aumais, G., Bernard, E. J., Bitton, A., Rivas, Manuel A., Cohen, A., Deslandres, C., Lahaie, R., Paré, P., Brant, S. R., Cho, J. H., Duerr, R. H., Stevens, Christine, Ahmad, T., Anderson, C. A., Annese, V., Baldassano, R. N., Balschun, T., Barclay, M., Barrett, J. C., Bayless, T. M., Bis, J. C., Alikashani, Azadeh, Brand, S., Bumpstead, S., Buning, C., Colombel, J. F., Cottone, M., D'Amato, M., D'Inca, R., Ladouceur, Martin, Daly, M. J., Denson, T., Dubinsky, M., Edwards, C., Ellinghaus, D., Florin, T., Franchimont, D., Franke, A., Gearry, R., Ellinghaus, David, Georges, M., Glas, J., Van Gossum, A., Griffiths, A. M., Guthery, S. L., Hakonarson, H., Haritunians, T., Hugot, J. P., de Jong, D. J., Jostins, L., Torkvist, Leif, Kugathasan, S., Kullak-Ublick, G., Latiano, A., Laukens, D., Lawrance, I., Lee, J., Lees, C. W., Lemann, M., Levine, A., Libioulle, C.

المساهمون: Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

المصدر: Plos Genetics, 9, 9, pp. e1003723
PLoS genetics, 9(9):e1003723. PUBLIC LIBRARY SCIENCE
PLoS Genetics, Vol 9, Iss 9, p e1003723 (2013)
PLoS Genetics
PLoS Genetics, 9(9)
Plos Genetics, 9, e1003723
PLOS genetics, 9 (9
Lees, C & Satsangi, J 2013, ' Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis ', PLoS Genetics, vol. 9, no. 9, pp. e1003723 . https://doi.org/10.1371/journal.pgen.1003723Test
PLoS genetics 9(9), e1003723 (2013). doi:10.1371/journal.pgen.1003723
PLOS GENETICS

مصطلحات موضوعية: Cancer Research, Génétique clinique, LIVER, Genome-wide association study, Inflammatory bowel disease, 0302 clinical medicine, Crohn Disease, GENETIC-VARIANTS, Medicine and Health Sciences, Ethnicity, UBIQUITIN LIGASES, Genetics(clinical), Genetics (clinical), Genetics, 0303 health sciences, Ecology, High-Throughput Nucleotide Sequencing, CROHN-DISEASE, CROHNS-DISEASE, 3. Good health, 030220 oncology & carcinogenesis, Medical genetics, Biologie, Research Article, EXPRESSION, medicine.medical_specialty, Canada, lcsh:QH426-470, SUSCEPTIBILITY LOCI, Evolution, Ubiquitin-Protein Ligases, Ethnic Groups, Evolution des espèces, Biology, Molecular gastro-enterology and hepatology Pathogenesis and modulation of inflammation [IGMD 2], Polymorphism, Single Nucleotide, 03 medical and health sciences, Behavior and Systematics, medicine, Humans, Genetic Predisposition to Disease, Ligase activity, MODULATION, Allele, GENOME-WIDE ASSOCIATION, Molecular Biology, Genotyping, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, Ecologie, Biologie moléculaire, Receptors, Interleukin, medicine.disease, NUCLEAR FACTOR 4-ALPHA, Genetic architecture, Cancérologie, CARD Signaling Adaptor Proteins, lcsh:Genetics, CELLS, Colitis, Ulcerative, INTESTINAL EPITHELIAL-CELLS, Genome-Wide Association Study, INFLAMMATORY-BOWEL-DISEASE

الوصف: Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (~14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. © 2013 Beaudoin et al.
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SCOPUS: ar.j
info:eu-repo/semantics/published

وصف الملف: application/pdf; 1 full-text file(s): application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2848aa5d583f624e11893cb2f15d02f6Test
https://hdl.handle.net/https://repository.ubn.ru.nl/handle/2066/125308Test

المؤلفون: Festen, E. A. M., Goyette, P., Scott, R., Annese, V., Zhernakova, A., Lian, J., Lefebvre, C., Brant, S. R., Cho, J. H., Silverberg, M. S., Taylor, K. D., de Jong, D. J., Stokkers, P. C., Mcgovern, D., Palmieri, O., Achkar, J-P, Xavier, R. J., Daly, M. J., Duerr, R. H., Wijmenga, C., Weersma, R. K., Rioux, J. D.

المصدر: Festen , E A M , Goyette , P , Scott , R , Annese , V , Zhernakova , A , Lian , J , Lefebvre , C , Brant , S R , Cho , J H , Silverberg , M S , Taylor , K D , de Jong , D J , Stokkers , P C , Mcgovern , D , Palmieri , O , Achkar , J-P , Xavier , R J , Daly , M J , Duerr , R H , Wijmenga , C , Weersma , R K & Rioux , ....

مصطلحات موضوعية: GENOME-WIDE ASSOCIATION, INFLAMMATORY-BOWEL-DISEASE, SYSTEMIC-LUPUS-ERYTHEMATOSUS, CELIAC-DISEASE, CROHNS-DISEASE, SUSCEPTIBILITY LOCI, BARRIER DEFECT, RISK VARIANTS, MYOSIN IXB, INTERLEUKIN-21

الوصف: Objectives: Genetic susceptibility is known to play a large part in the predisposition to the inflammatory bowel diseases (IBDs) known as Crohn's disease (CD) and ulcerative colitis (UC). The IL2/IL21 locus on 4q27 is known to be a common risk locus for inflammatory disease (shown in coeliac disease, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and psoriasis), while the roles that interleukin 2 (IL2) and IL21 play in the immune response also make them attractive candidates for IBD. The objective of this study was to test for association between the IL2/IL21 locus and the IBDs. Methods: The four single nucleotide polymorphisms (SNPs) in the IL2/IL21 locus most associated with coeliac disease were genotyped in 1590 subjects with IBD and 929 controls from The Netherlands, and then replicated in a North American cohort (2387 cases and 1266 controls) and an Italian cohort (805 cases and 421 controls), yielding a total of 4782 cases (3194 UC, 1588 CD) and 2616 controls. Allelic association testing and a pooled analysis using a Cochran-Mantel-Haenszel test were performed. Results: All four SNPs were strongly associated with UC in all three cohorts and reached genome-wide significance in the pooled analysis (rs13151961 p = 1.35x10(-10), rs13119723 p = 8.60x10(-8), rs6840978 p = 3.07x10(-8), rs6822844 p = 2.77x10(-9)). A moderate association with CD was also found in the pooled analysis (p value range 0.0016-9.86x10(-5)). Conclusions: A strong association for the IL2/IL21 locus with UC was found, which also confirms it as a general susceptibility locus for inflammatory disease.

العلاقة: https://research.rug.nl/en/publications/f4260c7a-0d77-45cf-a492-85c71a60ed5cTest

الإتاحة: https://doi.org/10.1136/gut.2008.166918Test
https://hdl.handle.net/11370/f4260c7a-0d77-45cf-a492-85c71a60ed5cTest
https://research.rug.nl/en/publications/f4260c7a-0d77-45cf-a492-85c71a60ed5cTest

المؤلفون: Weersma, R. K., Stokkers, P. C. F., van Bodegraven, A. A., van Hogezand, R. A., Verspaget, H. W., de Jong, D. J., van der Woude, C. J., Oldenburg, B., Linskens, R. K., Festen, E. A. M., van der Steege, G., Hommes, D. W., Crusius, J. B. A., Wijmenga, C., Nolte, I. M., Dijkstra, G.

المصدر: Weersma , R K , Stokkers , P C F , van Bodegraven , A A , van Hogezand , R A , Verspaget , H W , de Jong , D J , van der Woude , C J , Oldenburg , B , Linskens , R K , Festen , E A M , van der Steege , G , Hommes , D W , Crusius , J B A , Wijmenga , C , Nolte , I M , Dijkstra , G & Dutch Initiative on Crohn and Colitis 2009 , ' Molecular prediction of disease ....

مصطلحات موضوعية: INFLAMMATORY-BOWEL-DISEASE, GENOME-WIDE ASSOCIATION, ULCERATIVE-COLITIS, GENETIC-VARIATION, SUSCEPTIBILITY LOCI, VARIANTS, POLYMORPHISMS, AUTOPHAGY, MULTIPLE, ATG16L1

الوصف: Background: Crohn's disease and ulcerative colitis have a complex genetic background. We assessed the risk for both the development and severity of the disease by combining information from genetic variants associated with inflammatory bowel disease (IBD). Methods: We studied 2804 patients (1684 with Crohn's disease and 1120 with ulcerative colitis) and 1350 controls from seven university hospitals. Details of the phenotype were available for 1600 patients with Crohn's disease and for 800 with ulcerative colitis. Genetic association for disease susceptibility was tested for the nucleotide-binding and oligomerisation domain 2 gene (NOD2), the IBD5 locus, the Drosophila discs large homologue 5 and autophagy-related 16-like 1 genes (DLG5 and ATG16L1) and the interleukin 23 receptor gene (IL23R). Interaction analysis was performed for Crohn's disease using the most associated single nucleotide polymorphism (SNP) for each locus. Odds ratios were calculated in an ordinal regression analysis with the number of risk alleles as an independent variable to analyse disease development and severity. Results: Association with Crohn's disease was confirmed for NOD2, IBD5, DLG5, ATG16L1 and IL23R. Patients with Crohn's disease carry more risk alleles than controls (p = 3.85 x 10(-22)). Individuals carrying an increasing number of risk alleles have an increasing risk for Crohn's disease, consistent with an independent effects multiplicative model (trend analysis p = 4.25 x 10(-23)). Patients with Crohn's disease with a more severe disease course, operations or an age of onset below 40 years have more risk alleles compared to non-stricturing, non-penetrating behaviour (p = 0.0008), no operations (p = 0.02) or age of onset above 40 years (p = 0.028). Conclusion: Crohn's disease is a multigenic disorder. An increase in the number of risk alleles is associated with an increased risk for the development of Crohn's disease and with a more severe disease course. Combining information from the known common risk polymorphisms may enable ...

العلاقة: https://research.rug.nl/en/publications/ce48ca6d-a226-4611-abcb-95e92ccc05e0Test

الإتاحة: https://doi.org/10.1136/gut.2007.144865Test
https://hdl.handle.net/11370/ce48ca6d-a226-4611-abcb-95e92ccc05e0Test
https://research.rug.nl/en/publications/ce48ca6d-a226-4611-abcb-95e92ccc05e0Test

المؤلفون: Wapenaar, M. C., Monsuur, A. J., van Bodegraven, A. A., Weersma, R. K., Bevova, M. R., Linskens, R. K., Howdle, P., Holmes, G., Mulder, C. J., Dijkstra, G., van Heel, D. A., Wijmenga, C.

المصدر: Wapenaar , M C , Monsuur , A J , van Bodegraven , A A , Weersma , R K , Bevova , M R , Linskens , R K , Howdle , P , Holmes , G , Mulder , C J , Dijkstra , G , van Heel , D A & Wijmenga , C 2008 , ' Associations with tight junction genes PARD3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitis ' , Gut , vol. 57 , no. 4 , pp. 463-467 . https://doi.org/10.1136/gut.2007.133132Test

مصطلحات موضوعية: INFLAMMATORY-BOWEL-DISEASE, CROHNS-DISEASE, EPITHELIAL BARRIER, ALTERED EXPRESSION, ION-TRANSPORT, MYOSIN IXB, PERMEABILITY, DLG5, VARIANTS, GENETICS

الوصف: Background: Coeliac disease (gluten-sensitive enteropathy; GSE) and inflammatory bowel disease (IBD) are common gastrointestinal disorders. Both display enhanced intestinal permeability, initiated by gluten exposure (GSE) or bacterial interactions (IBD). Previous studies showed the association of both diseases with variants in MYO9B, presumably involved in epithelial permeability. Aim: It was hypothesised that genetic variants in tight junction genes might affect epithelial barrier function, thus contributing to a shared pathogenesis of GSE and IBD. Methods: This hypothesis was tested with a comprehensive genetic association analysis of 41 genes from the tight junction pathway, represented by 197 tag single nucleotide polymorphism (SNP) markers. Results: Two genes, PARD3 (two SNPs) and MAGI2 (two SNPs), showed weak association with GSE in a Dutch cohort. Replication in a British GSE cohort yielded significance for one SNP in PARD3 and suggestive associations for two additional SNPs, one each in PARD3 and MAGI2. Joint analysis of the British and Dutch data further substantiated the association for both PARD3 (rs10763976, p= 6.4x10(-5); OR 1.23, 95% CI 1.11 to 1.37) and MAGI2 (rs6962966, p= 7.6x10(-4); OR 1.19, 95% CI 1.08 to 1.32). Association was also observed in Dutch ulcerative colitis patients with MAGI2 ( rs6962966, p= 0.0036; OR 1.26, 95% CI 1.08 to 1.47), and suggestive association with PARD3 (rs4379776, p= 0.068). Conclusions: These results suggest that coeliac disease and ulcerative colitis may share a common aetiology through tight junction-mediated barrier defects, although the observations need further replication.

العلاقة: https://research.rug.nl/en/publications/77345cce-131c-4bf5-a01e-ca75542856d7Test

الإتاحة: https://doi.org/10.1136/gut.2007.133132Test
https://hdl.handle.net/11370/77345cce-131c-4bf5-a01e-ca75542856d7Test
https://research.rug.nl/en/publications/77345cce-131c-4bf5-a01e-ca75542856d7Test

المؤلفون: Weersma, R. K., Peters, F. T. M., Oostenbrug, L. E., van den Berg, A. P., van Haastert, M., Ploeg, R. J., Posthumus, M. D., Homan van der Heide, J. J., Jansen, P. L. M., van Dullemen, H. M.

المساهمون: Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Center for Liver, Digestive and Metabolic Diseases (CLDM), Other departments, Gastroenterology and Hepatology

المصدر: Alimentary Pharmacology & Therapeutics, 20(8), 843-850. Wiley
Alimentary pharmacology & therapeutics, 20(8), 843-850. Wiley-Blackwell

مصطلحات موضوعية: 6-MERCAPTOPURINE, MAINTENANCE, HYPERAMYLASEMIA, EFFICACY, TERM, THERAPY, THIOPURINE S-METHYLTRANSFERASE, RANDOMIZED-TRIAL, LUPUS NEPHRITIS, INFLAMMATORY-BOWEL-DISEASE

الوصف: BACKGROUND: Azathioprine is widely used in Crohn's disease. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Acute pancreatitis is rarely seen when azathioprine is used for other diseases than Crohn's disease. AIM: To survey side-effects of azathioprine after liver or renal transplantation, for systemic lupus erythematosis, Wegener's granulomatosis, autoimmune hepatitis, rheumatoid arthritis, ulcerative colitis or Crohn's disease. METHODS: A computerized search using the term 'azathioprine' or 'imuran' was performed on the Hospital Information System of the university hospital Groningen, resulting in 1564 patients matching our criteria. RESULTS: Eleven of 224 patients with Crohn's disease experienced acute pancreatitis (4.9%) compared with two of 129 (1.5%) with autoimmune hepatitis, two of 388 (0.5%) after renal transplantation, one of 254 (0.4%) after liver transplantation. Acute pancreatitis was more prevalent in Crohn's disease compared with any other disease. Azathioprine-toxicity necessitating withdrawal occurred significantly (P < 0,05) more in rheumatoid arthritis (78 of 317), ulcerative colitis (20 of 94) and Crohn's disease (52 of 224) compared with systemic lupus erythematosis (five of 73), Wegener's granulomatosis (six of 85), autoimmune hepatitis (eight of 129), after liver transplantation (17 of 254) and after renal transplantation (22 of 388). CONCLUSIONS: Acute pancreatitis is strongly associated with Crohn's disease and rarely occurs with other underlying conditions. Overall azathioprine-induced toxicity and the necessity of withdrawal is more common in inflammatory bowel disease and rheumatoid arthritis compared with other diseases.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::7813b996711572d0b3227ed1de813030Test
https://research.rug.nl/en/publications/4283c623-e6ed-4d50-94c8-e01ad6e78a26Test