Variants in CPA1 are strongly associated with early onset chronic pancreatitis.

Witt, H; Beer, S; Rosendahl, J; Chen, JM; Chandak, GR; Masamune, A; Bence, M; Szmola, R; Oracz, G; Macek, M; Bhatia, E; Steigenberger, S; Lasher, D; Bühler, F; Delaporte, C; Tebbing, J; Ludwig, M; Pilsak, C; Saum, K; Bugert, P; Masson, E; Paliwal, S; Bhaskar, S; Sobczynska-Tomaszewska, A; Bak, D; Balascák, I; Choudhuri, G; Nageshwar Reddy, D; Rao, GV; Thomas, V; Kume, K; Nakano, E; Kakuta, Y; Shimosegawa, T; Durko, L; Szabo, A; Schnúr, A; Hegyi, P; Rakonczay, Z; Pfützer, R; Schneider, A; Groneberg, DA; Braun, M; Schmidt, H; Witt, U; Friess, H; Algul, H; Landt, O; Schuelke, M; Kruger, R; Wiedenmann, B; Schmidt, F; Zimmer, KP; Kovacs, P; Stumvoll, M; Blüher, M; Müller, T; Janecke, A; Teich, N; Grützmann, R; Schulz, HU; Mössner, J; Keim, V; Löhr, M; Férec, C; Sahin-Tóth, M

doi:10.1038/ng.2730

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2013

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Title:: Variants in CPA1 are strongly associated with early onset chronic pancreatitis.
Document type:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Article
Author(s):: Witt, H; Beer, S; Rosendahl, J; Chen, JM; Chandak, GR; Masamune, A; Bence, M; Szmola, R; Oracz, G; Macek, M; Bhatia, E; Steigenberger, S; Lasher, D; Bühler, F; Delaporte, C; Tebbing, J; Ludwig, M; Pilsak, C; Saum, K; Bugert, P; Masson, E; Paliwal, S; Bhaskar, S; Sobczynska-Tomaszewska, A; Bak, D; Balascák, I; Choudhuri, G; Nageshwar Reddy, D; Rao, GV; Thomas, V; Kume, K; Nakano, E; Kakuta, Y; Shimosegawa, T; Durko, L; Szabo, A; Schnúr, A; Hegyi, P; Rakonczay, Z; Pfützer, R; Schneider, A; Groneberg, DA; Braun, M; Schmidt, H; Witt, U; Friess, H; Algul, H; Landt, O; Schuelke, M; Kruger, R; Wiedenmann, B; Schmidt, F; Zimmer, KP; Kovacs, P; Stumvoll, M; Blüher, M; Müller, T; Janecke, A; Teich, N; Grützmann, R; Schulz, HU; Mössner, J; Keim, V; Löhr, M; Férec, C; Sahin-Tóth, M «
Witt, H; Beer, S; Rosendahl, J; Chen, JM; Chandak, GR; Masamune, A; Bence, M; Szmola, R; Oracz, G; Macek, M; Bhatia, E; Steigenberger, S; Lasher, D; Bühler, F; Delaporte, C; Tebbing, J; Ludwig, M; Pilsak, C; Saum, K; Bugert, P; Masson, E; Paliwal, S; Bhaskar, S; Sobczynska-Tomaszewska, A; Bak, D; Balascák, I; Choudhuri, G; Nageshwar Reddy, D; Rao, GV; Thomas, V; Kume, K; Nakano, E; Kakuta, Y; Shimosegawa, T; Durko, L; Szabo, A; Schnúr, A; Hegyi, P; Rakonczay, Z; Pfützer, R; Schneider, A; Gronebe... »
Abstract:: 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. Functionally 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 × 10(-16)). The association was strongest in subjects aged <= 10 years (9.7%; OR = 84.0, P = 4.1 × 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.
Journal title abbreviation:: Nat Genet
Year:: 2013
Journal volume:: 45
Journal issue:: 10
Pages contribution:: 1216-20
Language:: eng
Fulltext / DOI:: doi:10.1038/ng.2730
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/23955596
Print-ISSN:: 1061-4036
TUM Institution:: Chirurgische Klinik und Poliklinik; Else Kröner-Fresenius-Zentrum für Ernährungsmedizin - Klinik für Ernährungsmedizin; II. Medizinische Klinik und Poliklinik (Gastroenterologie)
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