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1. The impact of the rs8005161 polymorphism on G protein-coupled receptor GPR65 (TDAG8) pH-associated activation in intestinal inflammation

Author

Tcymbarevich I, Eloranta J, Spalinger M, Cosin-Roger J, Lang S, Kullak-Ublick G, Wagner C, Seuwen K, Ruiz P, de Valliere C, Abdelrahman K, Ademi G, Aepli P, Thomas A, Anderegg C, Antonino A, Archanioti E, Arrigoni E, de Jong D, Balsiger B, Basturk P, Bauerfeind P, Becocci A, Belli D, Bengoa J, Biedermann L, Binek J, Blattmann M, Boehm S, Boldanova T, Borovicka J, Braegger C, Brand S, Brugger L, Brunner S, Buhr P, Burnand B, Burk S, Burri E, Buyse S, Cao D, Carstens O, Criblez D, Cunningham S, D'Angelo F, de Saussure P, Degen L, Delarive J, Doerig C, Dora B, Drerup S, Egger M, El-Wafa A, Engelmann M, Ezri J, Felley C, Fliegner M, Fournier N, Fraga M, Franc Y, Frei P, Frei R, Fried M, Froehlich F, Furlano R, Garzoni L, Geyer M, Girard L, Girardin M, Golay D, Good I, Bigler U, Gysi B, Haarer J, Halama M, Haldemann J, Heer P, Heimgartner B, Helbling B, Hengstler P, Herzog D, Hess C, Hessler R, Heyland K, Hinterleitner T, Hirschi C, Hruz P, Juillerat P, Khalid-de Bakker C, Kayser S, Keller C, Knellwolf-Grieger C, Knoblauch C, Kohler H, Koller R, Krieger-Grubel C, Kunzler P, Kusche R, Lehmann F, Macpherson A, Maillard M, Manz M, Marot A, Meier R, Meyenberger C, Meyer P, Michetti P, Misselwitz B, Mosler P, Mottet C, Muller C, Mullhaupt B, Musso L, Neagu M, Nichita C, Niess J, Nydegger A, Obialo N, Ollo D, Oropesa C, Peter U, Peternac D, Petit L, Pittet V, Pohl D, Porzner M, Preissler C, Raschle N, Rentsch R, Restellini A, Restellini S, Richterich J, Ris F, Risti B, Ritz M, Rogler G, Rohrich N, Rossel J, Rueger V, Rusticeanu M, Sagmeister M, Saner G, Sauter B, Sawatzki M, Scharl M, Schelling M, Schibli S, Schlauri H, Schluckebier D, Schmid D, Schmid-Uebelhart S, Schnegg J, Schoepfer A, Seematter V, Seibold F, Seirafi M, Semadeni G, Senning A, Sokollik C, Sommer J, Spalinger J, Spangenberger H, Stadler P, Staub P, Staudenmann D, Stenz V, Steuerwald M, Straumann A, Strebel B, Stulz A, Sulz M, Tatu A, Tempia-Caliera M, Thorens J, Truninger K, Tutuian R, Urfer P, Vavricka S, Viani F, Vogtlin J, Von Kanel R, Vouillamoz D, Vulliamy R, Wiesel P, Wiest R, Wohrle S, Zamora S, Zander S, Wylie T, Zeitz J, Zimmermann D, and Swiss IBD Cohort Study Grp

Subjects
UC, pH-sensing, cAMP, IBD, Acidic pH, RhoA, Inflammatory bowel diseases, CD
Abstract

BackgroundTissue inflammation in inflammatory bowel diseases (IBD) is associated with a decrease in local pH. The gene encoding G-protein-coupled receptor 65 (GPR65) has recently been reported to be a genetic risk factor for IBD. In response to extracellular acidification, proton activation of GPR65 stimulates cAMP and Rho signalling pathways. We aimed to analyse the clinical and functional relevance of the GPR65 associated single nucleotide polymorphism (SNP) rs8005161.Methods1138 individuals from a mixed cohort of IBD patients and healthy volunteers were genotyped for SNPs associated with GPR65 (rs8005161, rs3742704) and galactosylceramidase (rs1805078) by Taqman SNP assays. 2300 patients from the Swiss IBD Cohort Study (SIBDC) were genotyped for rs8005161 by mass spectrometry based SNP genotyping. IBD patients from the SIBDC carrying rs8005161 TT, CT, CC and non-IBD controls (CC) were recruited for functional studies. Human CD14+ cells were isolated from blood samples and subjected to an extracellular acidic pH shift, cAMP accumulation and RhoA activation were measured.ResultsIn our mixed cohort, but not in SIBDC patients, the minor variant rs8005161 was significantly associated with UC. In SIBDC patients, we observed a consistent trend in increased disease severity in patients carrying the rs8005161-TT and rs8005161-CT alleles. No significant differences were observed in the pH associated activation of cAMP production between IBD (TT, CT, WT/CC) and non-IBD (WT/CC) genotype carriers upon an acidic extracellular pH shift. However, we observed significantly impaired RhoA activation after an extracellular acidic pH shift in IBD patients, irrespective of the rs8005161 allele.ConclusionsThe T allele of rs8005161 might confer a more severe disease course in IBD patients. Human monocytes from IBD patients showed impaired pH associated RhoA activation upon an acidic pH shift.

Published
2019

2. Training primary care physicians in shared decision making for colorectal cancer screening : insights from a statewide organized Colorectal Cancer Screening Program in Switzerland

Author

Selby, K., Cornuz, J., Gachoud, D., Bulliard, JL., Nichita, C., Dorta, G., Ducros, C., and Auer, R.

Subjects
education
Abstract

An organized screening program in Vaud, Switzerland aims to offer the choice of fecal-immunological testing (FIT) and colonoscopy for colorectal cancer (CRC) screening -At baseline, wide variations between primary care physicians (PCPs) in prescription of FIT and colonoscopy. -Shared decision making (SDM) might reduce variations in care. AIM : Increase the proportion of PCPs who intend to offer their patients FIT and colonoscopy on an equal basis Methods : Training program in 2015 with before and after survey ; Parallel comparison through mailed survey to PCPs not attending ; Training program: 2 hour seminar with interactive quizzes, 8-minute video of SDM consultation, and distribution a decision aid and evidence synopsis.

Published
2017

4. A novel gene expression signature in peripheral blood mononuclear cells for early detection of colorectal cancer

Author

Nichita, C., Ciarloni, L., Monnier-Benoit, S., Hosseinian, S., Dorta, G., and Rüegg, Curzio

Subjects
neoplasms, digestive system diseases
Abstract

Background: Early detection and treatment of colorectal adenomatous polyps (AP) and colorectal cancer (CRC) is associated with decreased mortality for CRC. However, accurate, non-invasive and compliant tests to screen for AP and early stages of CRC are not yet available. A blood-based screening test is highly attractive due to limited invasiveness and high acceptance rate among patients.Aim: To demonstrate whether gene expression signatures in the peripheral blood mononuclear cells (PBMC) were able to detect the presence of AP and early stages CRC.Methods: A total of 85 PBMC samples derived from colonoscopy-verified subjects without lesion (controls) (n = 41), with AP (n = 21) or with CRC (n = 23) were used as training sets. A 42-gene panel for CRC and AP discrimination, including genes identified by Digital Gene Expression-tag profiling of PBMC, and genes previously characterised and reported in the literature, was validated on the training set by qPCR. Logistic regression analysis followed by bootstrap validation determined CRC- and AP-specific classifiers, which discriminate patients with CRC and AP from controls.Results: The CRC and AP classifiers were able to detect CRC with a sensitivity of 78% and AP with a sensitivity of 46% respectively. Both classifiers had a specificity of 92% with very low false-positive detection when applied on subjects with inflammatory bowel disease (n = 23) or tumours other than CRC (n = 14).Conclusion: This pilot study demonstrates the potential of developing a minimally invasive, accurate test to screen patients at average risk for colorectal cancer, based on gene expression analysis of peripheral blood mononuclear cells obtained from a simple blood sample.

Published
2014

5. [Gastrointestinal neuroendocrine tumors: pleomorphic and often ignored]

Author

Mh, Maillard, Hiroz P, Wagner D, John Prior, Boubaker A, Pralong F, Dorta G, and Nichita C

Subjects
Neuroendocrine Tumors, Biomarkers, Tumor, Humans, Antineoplastic Agents, Endoscopy, Digestive System, Gastrointestinal Neoplasms
Abstract

Although generally considered as rare, incidence of gastrointestinal neuroendocrine tumors (GI-NETs) is increasing. The general practitioner has thus to be familiar with the vast array of clinical presentations and the growing family of diagnostic tools that can be used. Symptoms can be related to their hormonal production, their local extent or a bleeding complication. The prognosis depends on the grade of tumor, its local extent at diagnosis and its localization. The diagnosis relies on radiologic, endoscopic and nuclear medicine strategies. In case of typical symptoms, a hormonal secretion should be sought. Treatment options are extensive and should be discussed in an interdisciplinary manner.

Published
2012

7. Clinical experience with Adalimumab in a multicenter Swiss cohort of patients with Crohn's disease

Author

Nichita, C.

Abstract

Background. Des études précédentes ont démontré l'efficacité et la tolérance de l'adalimumab chez les patients avec maladie de Crohn modérée ou sévère. Les patients qu'on rencontre dans la pratique quotidienne peuvent être différents des patients rigoureusement sélectionnés dans les études contrôlées.But. Dans ce travail, nous résumons notre expérience avec l'adalimumab durant une période de 3 ans.Méthodes. Nous avons analysé rétrospectivement les dossiers de 55 patients atteints d'une maladie de Crohn modérée ou sévère et traités par adalimumab dans les hôpitaux universitaires de Bâle, Zurich, Genève et Lausanne, ainsi que dans un cabinet médical à Olten. Les informations collectées étaient les suivantes : données démographiques, localisation, phénotype et durée de la maladie, traitements chirurgicaux précédents, traitements précédents par anti-TNF alpha ou immunosuppresseur, le traitement concomitant et l'activité de la maladie à la « baseline » et durant le traitement. La sévérité de la maladie à l'inclusion a été établie en utilisant le score Harvey- Bradshaw Index (HBI). Durant le traitement, la rémission a été définie avec un HBI

Published
2011

8. Buck-boost converters design for Ultracapacitors and lithium battery mixing in hybrid vehicle applications

Author

Mamadou Baïlo CAMARA, Gualous, H., Dakyo, B., Nichita, C., Makany, P., Groupe de Recherche en Electrotechnique et Automatique du Havre (GREAH), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU), Laboratoire Universitaire des Sciences Appliquées de Cherbourg (LUSAC), and Université de Caen Normandie (UNICAEN)

Subjects
Supercapacitor, Battery (electricity), business.industry, Computer science, Energy management, 020208 electrical & electronic engineering, [SPI.NRJ]Engineering Sciences [physics]/Electric power, Electrical engineering, Buck–boost converter, 020302 automobile design & engineering, 02 engineering and technology, Lithium battery, polynomial control, Converters, 7. Clean energy, Energy storage, [SPI]Engineering Sciences [physics], 0203 mechanical engineering, Control theory, 0202 electrical engineering, electronic engineering, information engineering, ultracapacitors, business, hybrid electric vehicle, Voltage
Abstract

This paper deals the embedded energy share between Supercapacitors (SC) and batteries. SC modules are dimensioned for peak power requirement and batteries provide the power in steady state. This last is directly connected to the DC-bus to maintain the voltage level between 38V and 60V. A buck-boost converter is interfaced between the SC and the DC-bus to manage the available energy. The originality of this study is focused on energy management strategy between SC and batteries. The proposed strategy is based on polynomial (RST) controller. Due to cost and available components (no optimized) such as batteries and semiconductors, the experimental test bench is designed in reduced scale. The used packs of SC include two modules of 10 cells in series for each one, and present a maximum voltage of 27V. The buck-boost converters control algorithms are implemented in PIC18F4431 microcontroller. Experimental and simulation results obtained from polynomial control strategy are presented, analyzed, and compared to proportional integral ones.

Published
2010
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20. The personality traits activity, self-reproach, and negative affect jointly predict clinical recurrence, depressive symptoms, and low quality of life in inflammatory bowel disease patients

Author

Sebastian Bruno Ulrich, Jordi, Brian Matthew, Lang, Jacqueline, Wyss, Bianca, Auschra, Bahtiyar, Yilmaz, Niklas, Krupka, Thomas, Greuter, Philipp, Schreiner, Luc, Biedermann, Martin, Preisig, Roland, von Känel, Gerhard, Rogler, Stefan, Begré, Benjamin, Misselwitz, Dorothee, Zimmermann, Swiss IBD cohort study group, Anderegg, C., Bauerfeind, P., Beglinger, C., Begré, S., Belli, D., Bengoa, J.M., Biedermann, L., Bigler, B., Binek, J., Blattmann, M., Boehm, S., Borovicka, J., Braegger, C.P., Brunner, N., Bühr, P., Burnand, B., Burri, E., Buyse, S., Cremer, M., Criblez, D.H., de Saussure, P., Degen, L., Delarive, J., Doerig, C., Dora, B., Dorta, G., Egger, M., Ehmann, T., El-Wafa, A., Engelmann, M., Ezri, J., Felley, C., Fliegner, M., Fournier, N., Fraga, M., Frei, P., Frei, R., Fried, M., Froehlich, F., Funk, C., Furlano, R.I., Gallot-Lavallée, S., Geyer, M., Girardin, M., Golay, D., Grandinetti, T., Gysi, B., Haack, H., Haarer, J., Helbling, B., Hengstler, P., Herzog, D., Hess, C., Heyland, K., Hinterleitner, T., Hiroz, P., Hirschi, C., Hruz, P., Iwata, R., Jost, R., Juillerat, P., Brondolo, V.K., Knellwolf, C., Knoblauch, C., Köhler, H., Koller, R., Krieger-Grübel, C., Kullak-Ublick, G., Künzler, P., Landolt, M., Lange, R., Lehmann, F.S., Macpherson, A., Maerten, P., Maillard, M.H., Manser, C., Manz, M., Marbet, U., Marx, G., Matter, C., McLin, V., Meier, R., Mendanova, M., Meyenberger, C., Michetti, P., Misselwitz, B., Moradpour, D., Morell, B., Mosler, P., Mottet, C., Müller, C., Müller, P., Müllhaupt, B., Münger-Beyeler, C., Musso, L., Nagy, A., Neagu, M., Nichita, C., Niess, J., Noël, N., Nydegger, A., Obialo, N., Oneta, C., Oropesa, C., Peter, U., Peternac, D., Petit, L.M., Piccoli-Gfeller, F., Pilz, J.B., Pittet, V., Raschle, N., Rentsch, R., Restellini, S., Richterich, J.P., Rihs, S., Ritz, M.A., Roduit, J., Rogler, D., Rogler, G., Rossel, J.B., Sagmeister, M., Saner, G., Sauter, B., Sawatzki, M., Schäppi, M., Scharl, M., Schelling, M., Schibli, S., Schlauri, H., Uebelhart, S.S., Schnegg, J.F., Schoepfer, A., Seibold, F., Seirafi, M., Semadeni, G.M., Semela, D., Senning, A., Sidler, M., Sokollik, C., Spalinger, J., Spangenberger, H., Stadler, P., Steuerwald, M., Straumann, A., Straumann-Funk, B., Sulz, M., Thorens, J., Tiedemann, S., Tutuian, R., Vavricka, S., Viani, F., Vögtlin, J., von Känel, R., Vonlaufen, A., Vouillamoz, D., Vulliamy, R., Wermuth, J., Werner, H., Wiesel, P., Wiest, R., Wylie, T., Zeitz, J., and Zimmermann, D.

Subjects
Cohort Studies, Humans, Personality Inventory, Quality of Life, Depression/epidemiology, Personality, Chronic Disease, Inflammatory Bowel Diseases, Five-factor model, Flares, IBD, NEO-FFI, Depression, Gastroenterology, 610 Medicine & health
Abstract

Background The bidirectional “gut-brain axis” has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). While the influence of stress and depressive symptoms on IBD is well-characterized, the role of personality remains insufficiently investigated. Methods Personality was assessed in 1154 Swiss IBD cohort study (SIBDCS) patients via the NEO-Five-Factor Inventory (NEO-FFI) as well as in 2600 participants of the population-based CoLaus¦PsyCoLaus cohort study (NEO-FFI-revised). The NEO-FFI subcomponents activity, self-reproach and negative affect were associated with higher IBD disease activity and were combined to a NEO-FFI risk score. This risk score was validated and its effect on clinical IBD course and psychological endpoints was analysed in time-to-event and cumulative incidence analyses. Results In time-to-event analyses, a high NEO-FFI risk score was predictive for the clinical endpoints of new extraintestinal manifestation [EIM, adjusted hazard ratio (aHR) = 1.64, corrected p value (q) = 0.036] and two established composite flare endpoints (aHR = 1.53–1.63, q = 0.003–0.006) as well as for the psychological endpoints depressive symptoms (aHR = 7.06, q q r = 0.03–0.14). Conclusions Personality assessed by the NEO-FFI contained considerable predictive power for disease recurrence, depressive symptoms and low quality of life in IBD patients. Nevertheless, the personalities of IBD patients did not substantially differ from the general population.

Published
2022
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21. Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

Author

Yoganathan, Priyatharsan, Rossel, Jean-Benoit, Jordi, Sebastian Bruno Ulrich, Franc, Yannick, Biedermann, Luc, Misselwitz, Benjamin, Hausmann, Martin, Rogler, Gerhard, Scharl, Michael, Frey-Wagner, Isabelle, Swiss IBD cohort study group, Marot, Astrid, Ris, Frédéric, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, University of Zurich, Frey-Wagner, Isabelle, Swiss IBD cohort study group, Abdelrahman, K., Ademi, G., Aepli, P., Thomas, A., Anderegg, C., Antonino, A.T., Archanioti, E., Arrigoni, E., de Jong, D.B., Balsiger, B., Bastürk, P., Bauerfeind, P., Becocci, A., Belli, D., Bengoa, J.M., Biedermann, L., Binek, J., Blattmann, M., Boehm, S., Boldanova, T., Borovicka, J., Braegger, C.P., Brand, S., Brügger, L., Brunner, S., Bühr, P., Burnand, B., Burk, S., Burri, E., Buyse, S., Cao, D.T., Carstens, O., Criblez, D.H., Cunningham, S., D'Angelo, F., de Saussure, P., Degen, L., Delarive, J., Doerig, C., Dora, B., Drerup, S., Egger, M., El-Wafa, A., Engelmann, M., Ezri, J., Felley, C., Fliegner, M., Fournier, N., Fraga, M., Franc, Y., Frei, P., Frei, R., Fried, M., Froehlich, F., Furlano, R.I., Garzoni, L., Geyer, M., Girard, L., Girardin, M., Golay, D., Good, I., Bigler, U.G., Gysi, B., Haarer, J., Halama, M., Haldemann, J., Heer, P., Heimgartner, B., Helbling, B., Hengstler, P., Herzog, D., Hess, C., Hessler, R., Heyland, K., Hinterleitner, T., Hirschi, C., Hruz, P., Juillerat, P., Bakker, C.K., Kayser, S., Keller, C., Grieger, C.K., Knoblauch, C., Köhler, H., Koller, R., Krieger-Grübel, C., Künzler, P., Kusche, R., Lehmann, F.S., Macpherson, A., Maillard, M.H., Manz, M., Marot, A., Meier, R., Meyenberger, C., Meyer, P., Michetti, P., Misselwitz, B., Mosler, P., Mottet, C., Müller, C., Müllhaupt, B., Musso, L., Neagu, M., Nichita, C., Niess, J., Nydegger, A., Obialo, N., Ollo, D., Oropesa, C., Peter, U., Peternac, D., Petit, L.M., Pittet, V., Pohl, D., Porzner, M., Preissler, C., Raschle, N., Rentsch, R., Restellini, A., Restellini, S., Richterich, J.P., Ris, F., Risti, B., Ritz, M.A., Rogler, G., Röhrich, N., Rossel, J.B., Rueger, V., Rusticeanu, M., Sagmeister, M., Saner, G., Sauter, B., Sawatzki, M., Scharl, M., Schelling, M., Schibli, S., Schlauri, H., Schluckebier, D., Schmid, D., Uebelhart, S.S., Schnegg, J.F., Schoepfer, A., Seematter, V., Seibold, F., Seirafi, M., Semadeni, G.M., Senning, A., Sokollik, C., Sommer, J., Spalinger, J., Spangenberger, H., Stadler, P., Staub, P., Staudenmann, D., Stenz, V., Steuerwald, M., Straumann, A., Strebel, B., Stulz, A., Sulz, M., Tatu, A., Tempia-Caliera, M., Thorens, J., Truninger, K., Tutuian, R., Urfer, P., Vavricka, S., Viani, F., Vögtlin, J., Von Känel, R., Vouillamoz, D., Vulliamy, R., Wiesel, P., Wiest, R., Wöhrle, S., Zamora, S., Zander, S., Wylie, T., Zeitz, J., and Zimmermann, D.

Subjects
Genotype, NLR Proteins, 610 Medicine & health, Single-nucleotide polymorphism, RC799-869, Disease, Polymorphism, Single Nucleotide, Inflammatory bowel disease, Pyrin domain, Cohort Studies, NLR Family, Pyrin Domain-Containing 3 Protein, Genetic variation, medicine, Humans, 2715 Gastroenterology, Genetic Predisposition to Disease, Allele, Gene, Genetic Association Studies, integumentary system, ddc:617, Clinical characteristics, 10179 Institute of Medical Microbiology, business.industry, Gastroenterology, Pyrin Domain, Single nucleotide polymorphisms, General Medicine, Diseases of the digestive system. Gastroenterology, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Colitis, Ulcerative/genetics, Switzerland, NLRP3 inflammasome, 10219 Clinic for Gastroenterology and Hepatology, 10036 Medical Clinic, Immunology, Colitis, Ulcerative, 610 Medizin und Gesundheit, business, Research Article
Abstract

Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

Published
2021
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22. Abdominal pain in patients with inflammatory bowel disease: association with single-nucleotide polymorphisms prevalent in irritable bowel syndrome and clinical management

Author

Luc Biedermann, Alexander Siebenhüner, Philipp Schreiner, René Roth, Benjamin Misselwitz, Martina Ledergerber, Brian M. Lang, Niklas Krupka, Thomas Greuter, Henriette Heinrich, Stefan Begré, Andreas Rickenbacher, Stephan R. Vavricka, Jonas Zeitz, Matthias Turina, Niko Beerenwinkel, Gerhard Rogler, Swiss IBD Cohort Study Group, Anderegg, C., Bauerfeind, P., Beglinger, C., Begré, S., Belli, D., Bengoa, J.M., Biedermann, L., Bigler, B., Binek, J., Blattmann, M., Boehm, S., Borovicka, J., Braegger, C.P., Brunner, N., Bühr, P., Burnand, B., Burri, E., Buyse, S., Cremer, M., Criblez, D.H., de Saussure, P., Degen, L., Delarive, J., Doerig, C., Dora, B., Dorta, G., Egger, M., Ehmann, T., El-Wafa, A., Engelmann, M., Ezri, J., Felley, C., Fliegner, M., Fournier, N., Fraga, M., Frei, P., Frei, R., Fried, M., Froehlich, F., Funk, C., Furlano, R.I., Gallot-Lavallée, S., Geyer, M., Girardin, M., Golay, D., Grandinetti, T., Gysi, B., Haack, H., Haarer, J., Helbling, B., Hengstler, P., Herzog, D., Hess, C., Heyland, K., Hinterleitner, T., Hiroz, P., Hirschi, C., Hruz, P., Iwata, R., Jost, R., Juillerat, P., Brondolo, V.K., Knellwolf, C., Knoblauch, C., Köhler, H., Koller, R., Krieger-Grübel, C., Kullak-Ublick, G., Künzler, P., Landolt, M., Lange, R., Lehmann, F.S., Macpherson, A., Maerten, P., Maillard, M.H., Manser, C., Manz, M., Marbet, U., Marx, G., Matter, C., McLin, V., Meier, R., Mendanova, M., Meyenberger, C., Michetti, P., Misselwitz, B., Moradpour, D., Morell, B., Mosler, P., Mottet, C., Müller, C., Müller, P., Müllhaupt, B., Münger-Beyeler, C., Musso, L., Nagy, A., Neagu, M., Nichita, C., Niess, J., Noël, N., Nydegger, A., Obialo, N., Oneta, C., Oropesa, C., Peter, U., Peternac, D., Petit, L.M., Piccoli-Gfeller, F., Pilz, J.B., Pittet, V., Raschle, N., Rentsch, R., Restellini, S., Richterich, J.P., Rihs, S., Ritz, M.A., Roduit, J., Rogler, D., Rogler, G., Rossel, J.B., Sagmeister, M., Saner, G., Sauter, B., Sawatzki, M., Schäppi, M., Scharl, M., Schelling, M., Schibli, S., Schlauri, H., Uebelhart, S.S., Schnegg, J.F., Schoepfer, A., Seibold, F., Seirafi, M., Semadeni, G.M., Semela, D., Senning, A., Sidler, M., Sokollik, C., Spalinger, J., Spangenberger, H., Stadler, P., Steuerwald, M., Straumann, A., Straumann-Funk, B., Sulz, M., Thorens, J., Tiedemann, S., Tutuian, R., Vavricka, S., Viani, F., Vögtlin, J., Von Känel, R., Vonlaufen, A., Vouillamoz, D., Vulliamy, R., Wermuth, J., Werner, H., Wiesel, P., Wiest, R., Wylie, T., Zeitz, J., Zimmermann, D., University of Zurich, and Misselwitz, Benjamin

Subjects
0301 basic medicine, Crohn’s disease, Abdominal pain, medicine.medical_specialty, 610 Medicine & health, Disease, Polymorphism, Single Nucleotide, Inflammatory bowel disease, Gastroenterology, Single-nucleotide polymorphisms, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Abdominal Pain/genetics, Colitis, Ulcerative/complications, Colitis, Ulcerative/genetics, Humans, Inflammatory Bowel Diseases/complications, Inflammatory Bowel Diseases/genetics, Irritable Bowel Syndrome/complications, Irritable Bowel Syndrome/genetics, Nucleotides, Irritable bowel syndrome, Ulcerative colitis, Internal medicine, medicine, 2715 Gastroenterology, lcsh:RC799-869, 10217 Clinic for Visceral and Transplantation Surgery, Crohn's disease, business.industry, General Medicine, Hepatology, Inflammatory Bowel Diseases, medicine.disease, 10219 Clinic for Gastroenterology and Hepatology, 030104 developmental biology, 10036 Medical Clinic, Colitis, Ulcerative, 030211 gastroenterology & hepatology, lcsh:Diseases of the digestive system. Gastroenterology, medicine.symptom, 610 Medizin und Gesundheit, business, Research Article, Cohort study
Abstract

Background Abdominal pain is a frequent symptom in patients with inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC). Pain can result from ongoing inflammation or functional disorders imitating irritable bowel syndrome (IBS). Several single-nucleotide polymorphisms (SNPs) have been associated with IBS. However, the impact of IBS genetics on the clinical course of IBD, especially pain levels of patients remains unclear. Methods Data of 857 UC and 1206 CD patients from the Swiss IBD Cohort Study were analysed. We tested the association of the maximum of the abdominal pain item of disease activity indices in UC and CD over the study period with 16 IBS-associated SNPs, using multivariate ANOVA models. Results In UC patients, the SNPs rs1042713 (located on the ADRB2 gene) and rs4663866 (close to the HES6 gene) were associated with higher abdominal pain levels (P = 0.044; P = 0.037, respectively). Abdominal pain was not associated with any markers of patient management in a model adjusted for confounders. In CD patients, higher levels of abdominal pain correlated with the number of physician contacts (P, BMC Gastroenterology, 21 (1), ISSN:1471-230X

Published
2021
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23. The impact of the rs8005161 polymorphism on G protein-coupled receptor GPR65 (TDAG8) pH-associated activation in intestinal inflammation

Author

Tcymbarevich, Irina V, Eloranta, Jyrki J, Rossel, Jean-Benoît, Obialo, Nicole, Spalinger, Marianne, Cosin-Roger, Jesus, Lang, Silvia, Kullak-Ublick, Gerd A, Wagner, Carsten A, Scharl, Michael, Seuwen, Klaus, Ruiz, Pedro A, Rogler, Gerhard, de Vallière, Cheryl, Misselwitz, Benjamin, Swiss IBD Cohort Study Group, Marot, Astrid, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, University of Zurich, de Vallière, Cheryl, Petit, Laëtitia Marie, Swiss IBD Cohort Study Group, Abdelrahman, K., Ademi, G., Aepli, P., Thomas, A., Anderegg, C., Antonino, A.T., Archanioti, E., Arrigoni, E., de Jong, D.B., Balsiger, B., Bastürk, P., Bauerfeind, P., Becocci, A., Belli, D., Bengoa, J.M., Biedermann, L., Binek, J., Blattmann, M., Boehm, S., Boldanova, T., Borovicka, J., Braegger, C.P., Brand, S., Brügger, L., Brunner, S., Bühr, P., Burnand, B., Burk, S., Burri, E., Buyse, S., Cao, D.T., Carstens, O., Criblez, D.H., Cunningham, S., D'Angelo, F., de Saussure, P., Degen, L., Delarive, J., Doerig, C., Dora, B., Drerup, S., Egger, M., El-Wafa, A., Engelmann, M., Ezri, J., Felley, C., Fliegner, M., Fournier, N., Fraga, M., Franc, Y., Frei, P., Frei, R., Fried, M., Froehlich, F., Furlano, R.I., Garzoni, L., Geyer, M., Girard, L., Girardin, M., Golay, D., Good, I., Bigler, U.G., Gysi, B., Haarer, J., Halama, M., Haldemann, J., Heer, P., Heimgartner, B., Helbling, B., Hengstler, P., Herzog, D., Hess, C., Hessler, R., Heyland, K., Hinterleitner, T., Hirschi, C., Hruz, P., Juillerat, P., Bakker, C.K., Kayser, S., Keller, C., Knellwolf, C., Knoblauch, C., Köhler, H., Koller, R., Krieger, C., Künzler, P., Kusche, R., Lehmann, F.S., Macpherson, A., Maillard, M.H., Manz, M., Marot, A., Meier, R., Meyenberger, C., Meyer, P., Michetti, P., Misselwitz, B., Mosler, P., Mottet, C., Müller, C., Müllhaupt, B., Musso, L., Neagu, M., Nichita, C., Niess, J., Nydegger, A., Obialo, N., Ollo, D., Oropesa, C., Peter, U., Peternac, D., Petit, L.M., Pittet, V., Pohl, D., Porzner, M., Preissler, C., Raschle, N., Rentsch, R., Restellini, A., Restellini, S., Richterich, J.P., Ris, F., Risti, B., Ritz, M.A., Rogler, G., Röhrich, N., Rossel, J.B., Rueger, V., Rusticeanu, M., Sagmeister, M., Saner, G., Sauter, B., Sawatzki, M., Scharl, M., Schelling, M., Schibli, S., Schlauri, H., Schluckebier, D., Schmid, D., Schmid, S., Schnegg, J.F., Schoepfer, A., Seematter, V., Seibold, F., Seirafi, M., Semadeni, G.M., Senning, A., Sokollik, C., Sommer, J., Spalinger, J., Spangenberger, H., Stadler, P., Staub, P., Staudenmann, D., Stenz, V., Steuerwald, M., Straumann, A., Strebel, B., Stulz, A., Sulz, M., Tatu, A., Tempia-Caliera, M., Thorens, J., Truninger, K., Tutuian, R., Urfer, P., Vavricka, S., Viani, F., Vögtlin, J., Von Känel, R., Vouillamoz, D., Vulliamy, R., Wiesel, P., Wiest, R., Wöhrle, S., Zamora, S., Zander, S., Wylie, T., Zeitz, J., and Zimmermann, D.

Subjects
Male, RHOA, pH-sensing, Lipopolysaccharide Receptors, 10052 Institute of Physiology, Receptors, G-Protein-Coupled, 0302 clinical medicine, UC, Risk Factors, Genotype, Adult, Alleles, Cyclic AMP/blood, Female, Galactosylceramidase/genetics, Genetic Predisposition to Disease, Homozygote, Humans, Hydrogen-Ion Concentration, Inflammatory Bowel Diseases/genetics, Inflammatory Bowel Diseases/physiopathology, Macrophages/immunology, Macrophages/metabolism, Middle Aged, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled/genetics, Receptors, G-Protein-Coupled/physiology, Signal Transduction, rhoA GTP-Binding Protein/blood, Acidic pH, CD, IBD, Inflammatory bowel diseases, RhoA, cAMP, Cyclic AMP, Receptor, ddc:618, biology, Gastroenterology, General Medicine, 3. Good health, 10219 Clinic for Gastroenterology and Hepatology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Research Article, Galactosylceramidase, medicine.medical_specialty, CD14, Single-nucleotide polymorphism, 610 Medicine & health, 03 medical and health sciences, Internal medicine, medicine, Extracellular, SNP, 2715 Gastroenterology, Allele, lcsh:RC799-869, business.industry, Macrophages, digestive system diseases, Endocrinology, 10036 Medical Clinic, 10199 Clinic for Clinical Pharmacology and Toxicology, biology.protein, lcsh:Diseases of the digestive system. Gastroenterology, business, rhoA GTP-Binding Protein
Abstract

Background Tissue inflammation in inflammatory bowel diseases (IBD) is associated with a decrease in local pH. The gene encoding G-protein-coupled receptor 65 (GPR65) has recently been reported to be a genetic risk factor for IBD. In response to extracellular acidification, proton activation of GPR65 stimulates cAMP and Rho signalling pathways. We aimed to analyse the clinical and functional relevance of the GPR65 associated single nucleotide polymorphism (SNP) rs8005161. Methods 1138 individuals from a mixed cohort of IBD patients and healthy volunteers were genotyped for SNPs associated with GPR65 (rs8005161, rs3742704) and galactosylceramidase (rs1805078) by Taqman SNP assays. 2300 patients from the Swiss IBD Cohort Study (SIBDC) were genotyped for rs8005161 by mass spectrometry based SNP genotyping. IBD patients from the SIBDC carrying rs8005161 TT, CT, CC and non-IBD controls (CC) were recruited for functional studies. Human CD14+ cells were isolated from blood samples and subjected to an extracellular acidic pH shift, cAMP accumulation and RhoA activation were measured. Results In our mixed cohort, but not in SIBDC patients, the minor variant rs8005161 was significantly associated with UC. In SIBDC patients, we observed a consistent trend in increased disease severity in patients carrying the rs8005161-TT and rs8005161-CT alleles. No significant differences were observed in the pH associated activation of cAMP production between IBD (TT, CT, WT/CC) and non-IBD (WT/CC) genotype carriers upon an acidic extracellular pH shift. However, we observed significantly impaired RhoA activation after an extracellular acidic pH shift in IBD patients, irrespective of the rs8005161 allele. Conclusions The T allele of rs8005161 might confer a more severe disease course in IBD patients. Human monocytes from IBD patients showed impaired pH associated RhoA activation upon an acidic pH shift. Electronic supplementary material The online version of this article (10.1186/s12876-018-0922-8) contains supplementary material, which is available to authorized users.

Published
2019
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