PT  - JOURNAL ARTICLE
AU  - Jonas Rosendahl
AU  - Holger Kirsten
AU  - Eszter Hegyi
AU  - Peter Kovacs
AU  - Frank Ulrich Weiss
AU  - Helmut Laumen
AU  - Peter Lichtner
AU  - Claudia Ruffert
AU  - Jian-Min Chen
AU  - Emmanuelle Masson
AU  - Sebastian Beer
AU  - Constantin Zimmer
AU  - Katharina Seltsam
AU  - Hana Algül
AU  - Florence Bühler
AU  - Marco J Bruno
AU  - Peter Bugert
AU  - Ralph Burkhardt
AU  - Giulia Martina Cavestro
AU  - Halina Cichoz-Lach
AU  - Antoni Farré
AU  - Josef Frank
AU  - Giovanni Gambaro
AU  - Sebastian Gimpfl
AU  - Harald Grallert
AU  - Heidi Griesmann
AU  - Robert Grützmann
AU  - Claus Hellerbrand
AU  - Péter Hegyi
AU  - Marcus Hollenbach
AU  - Sevastitia Iordache
AU  - Grazyna Jurkowska
AU  - Volker Keim
AU  - Falk Kiefer
AU  - Sebastian Krug
AU  - Olfert Landt
AU  - Milena Di Leo
AU  - Markus M Lerch
AU  - Philippe Lévy
AU  - Markus Löffler
AU  - Matthias Löhr
AU  - Maren Ludwig
AU  - Milan Macek
AU  - Nuria Malats
AU  - Ewa Malecka-Panas
AU  - Giovanni Malerba
AU  - Karl Mann
AU  - Julia Mayerle
AU  - Sonja Mohr
AU  - Rene H M te Morsche
AU  - Marie Motyka
AU  - Sebastian Mueller
AU  - Thomas Müller
AU  - Markus M Nöthen
AU  - Sergio Pedrazzoli
AU  - Stephen P Pereira
AU  - Annette Peters
AU  - Roland Pfützer
AU  - Francisco X Real
AU  - Vinciane Rebours
AU  - Monika Ridinger
AU  - Marcella Rietschel
AU  - Eva Rösmann
AU  - Adrian Saftoiu
AU  - Alexander Schneider
AU  - Hans-Ulrich Schulz
AU  - Nicole Soranzo
AU  - Michael Soyka
AU  - Peter Simon
AU  - James Skipworth
AU  - Felix Stickel
AU  - Konstantin Strauch
AU  - Michael Stumvoll
AU  - Pier Alberto Testoni
AU  - Anke Tönjes
AU  - Lena Werner
AU  - Jens Werner
AU  - Norbert Wodarz
AU  - Martin Ziegler
AU  - Atsushi Masamune
AU  - Joachim Mössner
AU  - Claude Férec
AU  - Patrick Michl
AU  - Joost P H Drenth
AU  - Heiko Witt
AU  - Markus Scholz
AU  - Miklós Sahin-Tóth
ED  - ,
TI  - Genome-wide association study identifies inversion in the <em>CTRB1-CTRB2</em> locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis
AID  - 10.1136/gutjnl-2017-314454
DP  - 2018 Oct 01
TA  - Gut
PG  - 1855--1863
VI  - 67
IP  - 10
4099  - http://gut.bmj.com/content/67/10/1855.short
4100  - http://gut.bmj.com/content/67/10/1855.full
SO  - Gut2018 Oct 01; 67
AB  - Objective Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus.Design 1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used.Results We replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk.Conclusion An inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.