Frank Ulrich Weiss1, Nico Hesselbarth2, Andrea Párniczky3, Dora Mosztbacher4, Felix Lämmerhirt1, Claudia Ruffert2, Peter Kovacs5, Sebastian Beer6, Katharina Seltsam6, Heidi Griesmann2, Richard Böhme2, Tom Kaune2, Marcus Hollenbach6, Hans-Ulrich Schulz7, Peter Simon1, Julia Mayerle8, Markus M Lerch1, Giulia Martina Cavestro9, Raffaella Alessia Zuppardo9, Milena Di Leo9, Pier Alberto Testoni9, Ewa Malecka-Panas10, Anita Gasirowska10, Stanislaw Głuszek11, Peter Bugert12, Andrea Szentesi13, Joachim Mössner6, Heiko Witt14, Patrick Michl2, Peter Hégyi15, Markus Scholz16, Jonas Rosendahl17. 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; Institute for Translational Medicine and First Department of Internal Medicine, University of Pécs, Pécs, Hungary. 4. First Department of Pediatrics, Semmelweis University, Budapest, Hungary. 5. Leipzig University Medical Center, IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany. 6. Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology, University of Leipzig, Leipzig, Germany. 7. Department of Surgery, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. 8. Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany; Department of Medicine II, University Hospital, Ludwig-Maximilians-University Munich, Germany. 9. Gastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy. 10. Department of Digestive Tract Diseases, Medical University of Łódź, Łódź, Poland. 11. Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland. 12. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service of Baden-Württemberg, Mannheim, Germany. 13. Institute for Translational Medicine and First Department of Internal Medicine, University of Pécs, Pécs, Hungary; First Department of Medicine, University of Szeged, Hungary. 14. Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Paediatric Nutritional Medicine, Technische Universität München (TUM), Freising, Germany. 15. Institute for Translational Medicine and First Department of Internal Medicine, University of Pécs, Pécs, Hungary; HAS-SZTE, Momentum Gastroenterology Multidisciplinary Research Group, Szeged, Hungary. 16. LIFE- Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany; Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. 17. Department of Internal Medicine I, Martin Luther University, Halle, Germany. Electronic address: jonas.rosendahl@uk-halle.de.
Abstract
BACKGROUND/ OBJECTIVES: Acute 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. METHODS: We 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. RESULTS: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for 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. CONCLUSIONS: The 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.
BACKGROUND/ OBJECTIVES: Acute 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. METHODS: We 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. RESULTS: Meta-analyses of all AP patients depicted significant (p-value < 0.05) associations for 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. CONCLUSIONS: The 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.
Authors: Anthony F Herzig; Emmanuelle Génin; David N Cooper; Emmanuelle Masson; Claude Férec; Jian-Min Chen Journal: Genes (Basel) Date: 2020-11-13 Impact factor: 4.096
Authors: Adam H Tencer; Khan L Cox; Gregory M Wright; Yi Zhang; Christopher J Petell; Brianna J Klein; Brian D Strahl; Joshua C Black; Michael G Poirier; Tatiana G Kutateladze Journal: Nat Commun Date: 2020-10-29 Impact factor: 14.919