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

Derikx, Monique H, MH; Kovacs, Peter, P; Scholz, Markus, M; Masson, Emmanuelle, E; Chen, Jian-Min, JM; Ruffert, Claudia, C; Lichtner, Peter, P; Te Morsche, Rene H M, RH; Cavestro, Giulia Martina, GM; Algül, Hana, H; Berg, Thomas, T; Bödeker, Hans, H; Blüher, Matthias, M; Bruno, Marco J, MJ; Buch, Stephan, S; Bugert, Peter, P; Cichoz-Lach, Halina, H; Dabrowski, Andrzej, A; Farré, Antoni, A; Frank, Josef, J; Gasiorowska, Anita, A; Geisz, Andrea, A; Goni, Elisabetta, E; Grothaus, Johannes, J; Grützmann, Robert, R; Haas, Stephan, S; Hampe, Jochen, J; Hellerbrand, Claus, C; Hegyi, Peter, P; Huster, Dominik, D; Ioana, Mihai, M; Iordache, Sevastitia, S; Jurkowska, Grazyna, G; Keim, Volker, V; Landt, Olfert, O; Di Leo, Milena, M; Lerch, Markus M, MM; Lévy, Philippe, P; Löhr, Matthias J, MJ; Macek, Milan, M; Malats, Nuria, N; Malecka-Panas, Ewa, E; Mariani, Alberto, A; Martorana, Davide, D; Mayerle, Julia, J; Mora, Josefina, J; Mössner, Joachim, J; Müller, Sebastian, S; Ockenga, Johann, J; Paderova, Jana, J; Pedrazzoli, Sergio, S; Pereira, Stephen P, SP; Pfützer, Roland, R; Real, Francisco X, FX; Rebours, Vinciane, V; Ridinger, Monika, M; Rietschel, Marcella, M; Rohde, Kerstin, K; Sack, Stephan, S; Saftoiu, Adrian, A; Schneider, Alexander, A; Schulz, Hans-Ulrich, HU; Soyka, Michael, M; Simon, Peter, P; Skipworth, James, J; Stickel, Felix, F; Stumvoll, Michael, M; Testoni, Pier Alberto, PA; Tönjes, Anke, A; Treiber, Matthias, M; Weiss, Frank Ulrich, FU; Werner, Jens, J; Wodarz, Norbert, N; Férec, Claude, C; Drenth, Joost P H, JP; Witt, Heiko, H; Rosendahl, Jonas, J     «

Derikx, Monique H, MH; Kovacs, Peter, P; Scholz, Markus, M; Masson, Emmanuelle, E; Chen, Jian-Min, JM; Ruffert, Claudia, C; Lichtner, Peter, P; Te Morsche, Rene H M, RH; Cavestro, Giulia Martina, GM; Algül, Hana, H; Berg, Thomas, T; Bödeker, Hans, H; Blüher, Matthias, M; Bruno, Marco J, MJ; Buch, Stephan, S; Bugert, Peter, P; Cichoz-Lach, Halina, H; Dabrowski, Andrzej, A; Farré, Antoni, A; Frank, Josef, J; Gasiorowska, Anita, A; Geisz, Andrea, A; Goni, Elisabetta, E; Grothaus, Johannes, J; Grütz...     »

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.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.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).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.     «

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.We studied 3062 patients with alcohol-related CP (ACP) or NACP and 5107 controls. Also, 1559 German...     »