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Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study


Derikx, Monique H; Kovacs, Peter; Scholz, Markus; Masson, Emmanuelle; Chen, Jian-Min; Ruffert, Claudia; Lichtner, Peter; Te Morsche, Rene H M; Cavestro, Giulia Martina; Algül, Hana; Berg, Thomas; Bödeker, Hans; Blüher, Matthias; Bruno, Marco J; Buch, Stephan; Bugert, Peter; Cichoz-Lach, Halina; Dabrowski, Andrzej; Farré, Antoni; Frank, Josef; Gasiorowska, Anita; Geisz, Andrea; Goni, Elisabetta; Grothaus, Johannes; Grützmann, Robert; Haas, Stephan; Hampe, Jochen; Hellerbrand, Claus; Hegyi, Peter; Huster, Dominik; Ioana, Mihai; Iordache, Sevastitia; Jurkowska, Grazyna; Keim, Volker; Landt, Olfert; Di Leo, Milena; Lerch, Markus M; Lévy, Philippe; Löhr, Matthias J; Macek, Milan; Malats, Nuria; Malecka-Panas, Ewa; Mariani, Alberto; Martorana, Davide; Mayerle, Julia; Mora, Josefina; Mössner, Joachim; Müller, Sebastian; Ockenga, Johann; Paderova, Jana; Pedrazzoli, Sergio; Pereira, Stephen P; Pfützer, Roland; Real, Francisco X; Rebours, Vinciane; Ridinger, Monika; Rietschel, Marcella; Rohde, Kerstin; Sack, Stephan; Saftoiu, Adrian; Schneider, Alexander; Schulz, Hans-Ulrich; Soyka, Michael; Simon, Peter; Skipworth, James; Stickel, Felix; Stumvoll, Michael; Testoni, Pier Alberto; Tönjes, Anke; Treiber, Matthias; Weiss, Frank Ulrich; Werner, Jens; Wodarz, Norbert; Férec, Claude; Drenth, Joost P H; Witt, Heiko; Rosendahl, Jonas (2015). Polymorphisms at PRSS1-PRSS2 and CLDN2-MORC4 loci associate with alcoholic and non-alcoholic chronic pancreatitis in a European replication study. Gut, 64(9):1426-1433.

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 PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 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 CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.

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 PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 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 CLDN2-MORC4 locus are associated with CP and strongly associate with ACP, but only rs7057398 with NACP in female patients.

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11 citations in Web of Science®
9 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2015
Deposited On:23 Jul 2015 07:33
Last Modified:05 Apr 2016 19:19
Publisher:BMJ Publishing Group
ISSN:0017-5749
Publisher DOI:https://doi.org/10.1136/gutjnl-2014-307453
PubMed ID:25253127

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