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Original article
Polymorphisms at PRSS1–PRSS2 and CLDN2–MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study
  1. Monique H Derikx1,*,
  2. Peter Kovacs2,*,
  3. Markus Scholz3,4,*,
  4. Emmanuelle Masson5,6,7,8,
  5. Jian-Min Chen5,6,7,8,
  6. Claudia Ruffert9,*,
  7. Peter Lichtner10,*,
  8. Rene H M te Morsche1,*,
  9. Giulia Martina Cavestro11,*,
  10. PanEuropean Working group on Alcoholic Chronic Pancreatitis members and collaborators,
  11. Claude Férec5,6,7,8,
  12. Joost P H Drenth1,*,
  13. Heiko Witt12,*,
  14. Jonas Rosendahl9,*
  1. 1Department of Gastroenterology and Hepatology, Radboud UMC, Nijmegen, The Netherlands
  2. 2Integrated Research and Treatment Centre (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany
  3. 3Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
  4. 4LIFE- Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
  5. 5Institut National de la Santé et de la Recherche Médicale (INSERM), U1078, Brest, France
  6. 6Etablissement Français du Sang (EFS)—Bretagne, Brest, France
  7. 7Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO), Brest, France
  8. 8Laboratoire de Génétique Moléculaire et d'Histocompatibilité, Centre Hospitalier Universitaire (CHU) Brest, Hôpital Morvan, Brest, France
  9. 9Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany
  10. 10Institute of Human Genetics, Helmholtz Centre Munich, German Research Centre for Environmental Health, Neuherberg, Germany
  11. 11Unità Operativa di Gastroenterologia ed Endoscopia Digestiva, Università Vita Salute San Raffaele e IRCCS Ospedale San Raffaele, Milan, Italy
  12. 12Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Zentralinstitut für Ernährungs- und Lebensmittelforschung (ZIEL) & Paediatric Nutritional Medicine, Technische Universität München (TUM), Munich, Germany
  1. Correspondence to Dr Jonas Rosendahl, Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University Clinic of Leipzig, Liebigstraße 20, Leipzig 04103, Germany; jonas.rosendahl{at}medizin.uni-leipzig.de

Abstract

Objective Several genetic risk factors have been identified for non-alcoholic chronic pancreatitis (NACP). A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4). We aimed to refine these findings in a large European cohort.

Design We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German patients with alcohol-associated cirrhosis or alcohol dependence were included for comparison. We performed several meta-analyses to examine genotype–phenotype relationships.

Results Association with ACP was found for rs10273639 (OR, 0.63; 95% CI 0.55 to 0.72). ACP was also associated with variants rs7057398 and rs12688220 in men (OR, 2.26; 95% CI 1.94 to 2.63 and OR, 2.66; 95% CI 2.21 to 3.21, respectively) and in women (OR, 1.57; 95% CI 1.14 to 2.18 and OR 1.71; 95% CI 1.41 to 2.07, respectively). Similar results were obtained when German patients with ACP were compared with those with alcohol-associated cirrhosis or alcohol dependence. In the overall population of patients with NACP, association with rs10273639 was absent (OR, 0.93; 95% CI 0.79 to 1.01), whereas rs7057398 of the X chromosomal single nucleotide polymorphisms was associated with NACP in women only (OR, 1.32; 95% CI 1.15 to 1.51).

Conclusions The single-nucleotide polymorphisms rs10273639 at the PRSS1–PRSS2 locus and rs7057398 and rs12688220 at the CLDN2MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.

  • CHRONIC PANCREATITIS
  • GENETIC POLYMORPHISMS
  • PANCREATITIS
  • TRYPSINOGEN

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