Variants in CPA1 are strongly associated with early onset chronic pancreatitis

Heiko Witt, Sebastian Beer, Jonas Rosendahl, Jian Min Chen, Giriraj Ratan Chandak, Atsushi Masamune, Melinda Bence, Richárd Szmola, Grzegorz Oracz, Milan Macek, Eesh Bhatia, Sandra Steigenberger, Denise Lasher, Florence Bühler, Catherine Delaporte, Johanna Tebbing, Maren Ludwig, Claudia Pilsak, Karolin Saum, Peter BugertEmmanuelle Masson, Sumit Paliwal, Seema Bhaskar, Agnieszka Sobczynska-Tomaszewska, Daniel Bak, Ivan Balascak, Gourdas Choudhuri, D. Nageshwar Reddy, G. Venkat Rao, Varghese Thomas, Kiyoshi Kume, Eriko Nakano, Yoichi Kakuta, Tooru Shimosegawa, Lukasz Durko, András Szabó, Andrea Schnúr, Péter Hegyi, Zoltán Rakonczay, Roland Pfützer, Alexander Schneider, David Alexander Groneberg, Markus Braun, Hartmut Schmidt, Ulrike Witt, Helmut Friess, Hana Algül, Olfert Landt, Markus Schuelke, Renate Krüger, Bertram Wiedenmann, Frank Schmidt, Klaus Peter Zimmer, Peter Kovacs, Michael Stumvoll, Matthias Blüher, Thomas Müller, Andreas Janecke, Niels Teich, Robert Grützmann, Hans Ulrich Schulz, Joachim Mössner, Volker Keim, Matthias Löhr, Claude Férec, Miklós Sahin-Tóth

研究成果: Article査読

168 被引用数 (Scopus)

抄録

Chronic pancreatitis is an inflammatory disorder of the pancreas. We analyzed CPA1, encoding carboxypeptidase A1, in subjects with nonalcoholic chronic pancreatitis (cases) and controls in a German discovery set and three replication sets. unctionally impaired variants were present in 29/944 (3.1%) German cases and 5/3,938 (0.1%) controls (odds ratio (OR) = 24.9, P = 1.5 X 10-16). The association was strongest in subjects aged =10 years (9.7%; OR = 84.0, P = 4.1 X 10-24). In the replication sets, defective CPA1 variants were present in 8/600 (1.3%) cases and 9/2,432 (0.4%) controls from Europe (P = 0.01), 5/230 (2.2%) cases and 0/264 controls from India (P = 0.02) and 5/247 (2.0%) cases and 0/341 controls from Japan (P = 0.013). The mechanism by which CPA1 variants confer increased pancreatitis risk may involve misfolding-induced endoplasmic reticulum stress rather than elevated trypsin activity, as is seen with other genetic risk factors for this disease.

本文言語English
ページ(範囲)1216-1220
ページ数5
ジャーナルNature Genetics
45
10
DOI
出版ステータスPublished - 2013 10

ASJC Scopus subject areas

  • 遺伝学

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