PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Rosendahl, J.* ; Kirsten, H.* ; Hegyi, E.* ; Kovacs, P.* ; Weiss, F.U.* ; Laumen, H.* ; Lichtner, P. ; Ruffert, C.* ; Chen, J.M.* ; Masson, E.* ; Beer, S.* ; Zimmer, C.* ; Seltsam, K.* ; Algül, H.* ; Bühler, F.* ; Bruno, M.J.* ; Bugert, P.* ; Burkhardt, R.* ; Cavestro, G.M.* ; Cichoz-Lach, H.* ; Farré, A.* ; Frank, J.* ; Gambaro, G.* ; Gimpfl, S.* ; Grallert, H. ; Griesmann, H.* ; Grützmann, R.* ; Hellerbrand, C.* ; Hegyi, P.* ; Hollenbach, M.* ; Iordache, S.* ; Jurkowska, G.* ; Keim, V.* ; Kiefer, F.* ; Krug, S.* ; Landt, O.* ; Leo, M.D.* ; Lerch, M.M.* ; Lévy, P.* ; Löffler, M.* ; Löhr, M.* ; Ludwig, M.* ; Macek, M.* ; Malats, N.* ; Malecka-Panas, E.* ; Malerba, G.* ; Mann, K.* ; Mayerle, J.* ; Mohr, S.* ; Te Morsche, R.H.M.* ; Motyka, M.* ; Mueller, S.* ; Müller, T.* ; Nöthen, M.M.* ; Pedrazzoli, S.* ; Pereira, S.P.* ; Peters, A. ; Pfützer, R.* ; Real, F.X.* ; Rebours, V.* ; Ridinger, M.* ; Rietschel, M.* ; Rösmann, E.* ; Saftoiu, A.* ; Schneider, A.* ; Schulz, H.U.* ; Soranzo, N.* ; Soyka, M.* ; Simon, P.* ; Skipworth, J.* ; Stickel, F.* ; Strauch, K. ; Stumvoll, M.* ; Testoni, P.A.* ; Tönjes, A.* ; Werner, L.* ; Werner, J.* ; Wodarz, N.* ; Ziegler, M.* ; Masamune, A.* ; Mössner, J.* ; Férec, C.* ; Michl, P.* ; P H Drenth, J.* ; Witt, H.* ; Scholz, M.* ; Sahin-Tóth, M.*

Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis.

Gut 67, 1855–186 (2018)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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 16.6kb 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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
17.016
3.832
54
68
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genome Wide Association Study ; Chronic Pancreatitis ; Genetic Rearrangement; Hereditary Pancreatitis; Cationic Trypsinogen; Variants; Prss1-prss2; Gene; Inhibitor; Mutation
Sprache englisch
Veröffentlichungsjahr 2018
Prepublished im Jahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 0017-5749
e-ISSN 1468-3288
Zeitschrift Gut (eGut)
Quellenangaben Band: 67, Heft: 10, Seiten: 1855–186 Artikelnummer: , Supplement: ,
Verlag BMJ Publishing Group
Verlagsort British Med Assoc House, Tavistock Square, London Wc1h 9jr, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
CF Genomics (CF-GEN)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
POF Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504090-001
A-632700-001
G-504091-002
G-504000-010
G-504100-001
G-501900-402
G-504000-001
G-500700-001
DOI 10.1136/gutjnl-2017-314454
WOS ID WOS:000445171800015
Scopus ID 85053117090
PubMed ID 28754779
Erfassungsdatum 2017-08-03
[➜Korrektur melden]