Common variants in the CLDN2-MORC4 and PRSS1-PRSS2 loci confer susceptibility to acute pancreatitis |
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| Authors: | Frank Ulrich Weiss Nico Hesselbarth Andrea Párniczky Dora Mosztbacher Felix Lämmerhirt Claudia Ruffert Peter Kovacs Sebastian Beer Katharina Seltsam Heidi Griesmann Richard Böhme Tom Kaune Marcus Hollenbach Hans-Ulrich Schulz Peter Simon Julia Mayerle Markus M. Lerch Giulia Martina Cavestro Jonas Rosendahl |
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| Affiliation: | 1. Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany;2. Department of Internal Medicine I, Martin Luther University, Halle, Germany;3. Heim Pál Children''s Hospital, Budapest, Hungary;4. Institute for Translational Medicine and First Department of Internal Medicine, University of Pécs, Pécs, Hungary;5. First Department of Pediatrics, Semmelweis University, Budapest, Hungary;6. Leipzig University Medical Center, IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany;g. Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology, University of Leipzig, Leipzig, Germany;h. Department of Surgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany;i. Department of Medicine II, University Hospital, Ludwig-Maximilians-University Munich, Germany;j. Gastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy;k. Department of Digestive Tract Diseases, Medical University of ?ód?, ?ód?, Poland;l. Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland;m. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service of Baden-Württemberg, Mannheim, Germany;n. First Department of Medicine, University of Szeged, Hungary;o. Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Paediatric Nutritional Medicine, Technische Universität München (TUM), Freising, Germany;p. HAS-SZTE, Momentum Gastroenterology Multidisciplinary Research Group, Szeged, Hungary;q. LIFE- Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany;r. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany |
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| Abstract: | Background/ObjectivesAcute pancreatitis (AP) is one of the most common gastrointestinal disorders often requiring hospitalization. Frequent aetiologies are gallstones and alcohol abuse. In contrast to chronic pancreatitis (CP) few robust genetic associations have been described. Here we analysed whether common variants in the CLDN2-MORC4 and the PRSS1-PRSS2 locus that increase recurrent AP and CP risk associate with AP.MethodsWe screened 1462 AP patients and 3999 controls with melting curve analysis for SNPs rs10273639 (PRSS1-PRSS2), rs7057398 (RIPPLY), and rs12688220 (MORC4). Calculations were performed for the overall group, aetiology, and gender sub-groups. To examine genotype-phenotype relationships we performed several meta-analyses.ResultsMeta-analyses of all AP patients depicted significant (p-value?rs10273639 (odds ratio (OR) 0.88, 95% confidence interval (CI) 0.81–0.97, p-value 0.01), rs7057398 (OR 1.27, 95% CI 1.07–1.5, p-value 0.005), and rs12688220 (OR 1.32, 95% CI 1.12–1.56, p-value 0.001). For the different aetiology groups a significant association was shown for rs10273639 (OR 0.76, 95% CI 0.63–0.92, p-value 0.005), rs7057398 (OR 1.43, 95% CI 1.07–1.92, p-value 0.02), and rs12688220 (OR 1.44, 95% CI 1.07–1.93, p-value 0.02) in the alcoholic sub-group only.ConclusionsThe association of CP risk variants with different AP aetiologies, which is strongest in the alcoholic AP group, might implicate common pathomechanisms most likely between alcoholic AP and CP. |
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