Dataset Information

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

ABSTRACT:

Objective

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.

SUBMITTER: Rygiel AM

PROVIDER: S-EPMC9250292 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Rygiel Agnieszka Magdalena AM Unger Lara Sophie LS Sörgel Franziska Lena FL Masson Emmanuelle E Matsumoto Ryotaro R Ewers Maren M Chen Jian-Min JM Bugert Peter P Buscail Louis L Gambin Tomasz T Oracz Grzegorz G Winiewska-Szajewska Maria M Mianowska Agnieszka A Poznanski Jarosław J Kosińska Joanna J Stawinski Piotr P Płoski Rafał R Koziel Dorota D Gluszek Stanisław S Laumen Helmut H Lindgren Fredrik F Löhr J Matthias JM Orekhova Anna A Rebours Vinciane V Rosendahl Jonas J Párniczky Andrea A Hegyi Péter P Sasaki Akira A Kataoka Fumiya F Tanaka Yu Y Hamada Shin S Sahin-Tóth Miklós M Hegyi Eszter E Férec Claude C Masamune Atsushi A Witt Heiko H

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 20220501 5

<h4>Objective</h4>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.<h4>Design</h4>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 sequence ...[more]

PMID: 35589511

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Dataset Information

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

Objective

Design

Results

Conclusion

Publications

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

Similar Datasets

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