title: Variants in CPA1 are strongly associated with early onset chronic pancreatitis.
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.
authors: 1] Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Technische Universität München (TUM), Freising, Germany. [2] Zentralinstitut für Ernährungs- und Lebensmittelforschung (ZIEL), TUM, Freising, Germany. [3] Department of Pediatrics, Klinikum Rechts der Isar (MRI), TUM, Munich, Germany.
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authors: Beer
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authors: Rosendahl
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authors: JM
authors: Chen
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authors: Chandak
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authors: Saum
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authors: Bugert
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authors: Masson
authors: Sumit
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authors: Paliwal
authors: Seema
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authors: Bhaskar
authors: Agnieszka
authors: A
authors: Sobczynska-Tomaszewska
authors: Daniel
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authors: Bak
authors: Ivan
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authors: Balascak
authors: Gourdas
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authors: Choudhuri
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authors: Nageshwar Reddy
authors: G Venkat
authors: GV
authors: Rao
authors: Varghese
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authors: Thomas
authors: Kiyoshi
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authors: Kume
authors: Eriko
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authors: Nakano
authors: Yoichi
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authors: Kakuta
authors: Tooru
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authors: Shimosegawa
authors: Lukasz
authors: L
authors: Durko
authors: András
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authors: Szabó
authors: Andrea
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authors: Schnúr
authors: Péter
authors: P
authors: Hegyi
authors: Zoltán
authors: Z
authors: Rakonczay
authors: Roland
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authors: Pfützer
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authors: David Alexander
authors: DA
authors: Groneberg
authors: Markus
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authors: Braun
authors: Hartmut
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authors: Schmidt
authors: Ulrike
authors: U
authors: Witt
authors: Helmut
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authors: Friess
authors: Hana
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authors: Algül
authors: Olfert
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authors: Landt
authors: Markus
authors: M
authors: Schuelke
authors: Renate
authors: R
authors: Krüger
authors: Bertram
authors: B
authors: Wiedenmann
authors: Frank
authors: F
authors: Schmidt
authors: Klaus-Peter
authors: KP
authors: Zimmer
authors: Peter
authors: P
authors: Kovacs
authors: Michael
authors: M
authors: Stumvoll
authors: Matthias
authors: M
authors: Blüher
authors: Thomas
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authors: Müller
authors: Andreas
authors: A
authors: Janecke
authors: Niels
authors: N
authors: Teich
authors: Robert
authors: R
authors: Grützmann
authors: Hans-Ulrich
authors: HU
authors: Schulz
authors: Joachim
authors: J
authors: Mössner
authors: Volker
authors: V
authors: Keim
authors: Matthias
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authors: Löhr
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mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D043422:Carboxypeptidases A / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D020022:Genetic Predisposition to Disease; D006801:Humans; D050500:Pancreatitis, Chronic / Q000235:genetics*; D055815:Young Adult
chemical_list: D043422:Carboxypeptidases A
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