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Variants in the pancreatic CUB and zona pellucida-like domains 1 (CUZD1) gene in early-onset chronic pancreatitis - A possible new susceptibility gene.

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cris.lastimport.scopus2024-02-12T20:41:46Z
dc.abstract.enObjective: Non-alcoholic chronic pancreatitis (NACP) frequently develops in the setting of genetic susceptibility associated with alterations in genes that are highly expressed in the pancreas. However, the genetic basis of NACP remains unresolved in a significant number of patients warranting a search for further risk genes. Design: We analyzed CUZD1, which encodes the CUB and zona pellucida-like domains 1 protein that is found in high levels in pancreatic acinar cells. We sequenced the coding region in 1163 European patients and 2018 European controls. In addition, we analyzed 297 patients and 1070 controls from Japan. We analyzed secretion of wild-type and mutant CUZD1 from transfected cells using Western blotting. Results: In the European cohort, we detected 30 non-synonymous variants. Using different prediction tools (SIFT, CADD, PROVEAN, PredictSNP) or the combination of these tools, we found accumulation of predicted deleterious variants in patients (p-value range 0.002–0.013; OR range 3.1–5.2). No association was found in the Japanese cohort, in which 13 non-synonymous variants were detected. Functional studies revealed >50% reduced secretion of 7 variants, however, these variants were not significantly enriched in European CP patients. Conclusion: Our data indicate that CUZD1 might be a novel susceptibility gene for NACP. How these variants predispose to pancreatitis remains to be elucidated.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorOracz, Grzegorz
dc.contributor.authorPoznański, Jarosław
dc.contributor.authorWitt, Heiko
dc.contributor.authorMasamune, Atsushi
dc.contributor.authorFérec, Claude
dc.contributor.authorHegyi, Eszter
dc.contributor.authorSahin-Tóth, Miklós
dc.contributor.authorHamada, Shin
dc.contributor.authorTanaka, Yu
dc.contributor.authorKataoka, Fumiya
dc.contributor.authorSasaki, Akira
dc.contributor.authorHegyi, Péter
dc.contributor.authorPárniczky, Andrea
dc.contributor.authorRosendahl, Jonas
dc.contributor.authorRebours, Vinciane
dc.contributor.authorOrekhova, Anna
dc.contributor.authorLöhr, J. Matthias
dc.contributor.authorLindgren, Fredrik
dc.contributor.authorLaumen, Helmut
dc.contributor.authorGluszek, Stanisław
dc.contributor.authorKoziel, Dorota
dc.contributor.authorPłoski, Rafał
dc.contributor.authorStawinski, Piotr
dc.contributor.authorKosińska, Joanna
dc.contributor.authorMianowska, Agnieszka
dc.contributor.authorWiniewska-Szajewska, Maria
dc.contributor.authorGambin, Tomasz
dc.contributor.authorBuscail, Louis
dc.contributor.authorBugert, Peter
dc.contributor.authorChen, Jian-Min
dc.contributor.authorEwers, Maren
dc.contributor.authorMatsumoto, Ryotaro
dc.contributor.authorMasson, Emmanuelle
dc.contributor.authorSörgel, Franziska Lena
dc.contributor.authorUnger, Lara Sophie
dc.contributor.authorRygiel, Agnieszka Magdalena
dc.date.accessioned2024-01-26T11:45:39Z
dc.date.available2024-01-26T11:45:39Z
dc.date.issued2022
dc.description.financeNie dotyczy
dc.description.number5
dc.description.volume22
dc.identifier.doi10.1016/J.PAN.2022.04.015
dc.identifier.issn1424-3903
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/124547
dc.identifier.weblinkhttps://www.sciencedirect.com/science/article/pii/S1424390322001661#kwrds0010
dc.languageeng
dc.pbn.affiliationphysical sciences
dc.relation.ispartofPancreatology
dc.relation.pages564-571
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enCUZD1
dc.subject.enZymogen granule
dc.subject.enChronic pancreatitis
dc.subject.enGenetics
dc.titleVariants in the pancreatic CUB and zona pellucida-like domains 1 (CUZD1) gene in early-onset chronic pancreatitis - A possible new susceptibility gene.
dc.typeJournalArticle
dspace.entity.typePublication