title: A common variant of PNPLA3 (p.I148M) is not associated with alcoholic chronic pancreatitis.
abstract: BACKGROUND
  Chronic pancreatitis (CP) is an inflammatory disease that in some patients leads to exocrine and endocrine dysfunction. In industrialized countries the most common aetiology is chronic alcohol abuse. Descriptions of associated genetic alterations in alcoholic CP are rare. However, a common PNPLA3 variant (p.I148M) is associated with the development of alcoholic liver cirrhosis (ALC). Since, alcoholic CP and ALC share the same aetiology PNPLA3 variant (p.I148M) possibly influences the development of alcoholic CP.
  
  
  METHODS
  Using melting curve analysis we genotyped the variant in 1510 patients with pancreatitis or liver disease (961 German and Dutch alcoholic CP patients, 414 German patients with idiopathic or hereditary CP, and 135 patients with ALC). In addition, we included in total 2781 healthy controls in the study.
  
  
  RESULTS
  The previously published overrepresentation of GG-genotype was replicated in our cohort of ALC (p-value <0.0001, OR 2.3, 95% CI 1.6-3.3). Distributions of genotype and allele frequencies of the p.I148M variant were comparable in patients with alcoholic CP, idiopathic and hereditary CP and in healthy controls.
  
  
  CONCLUSIONS
  The absence of an association of PNPLA3 p.I148M with alcoholic CP seems not to point to a common pathway in the development of alcoholic CP and alcoholic liver cirrhosis.
authors.affiliation: Division of Gastroenterology and Rheumatology, Department for Internal Medicine, Neurology and Dermatology, University of Leipzig, Leipzig, Germany. jonas.rosendahl@medizin.uni-leipzig.de
authors.forename: Jonas
authors.initials: J
authors.lastname: Rosendahl
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Dorit
authors.initials: D
authors.lastname: Schleinitz
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Johannes
authors.initials: J
authors.lastname: Wiegand
authors.forename: Claudia
authors.initials: C
authors.lastname: Ruffert
authors.forename: Moritz
authors.initials: M
authors.lastname: Jesinghaus
authors.forename: Robert
authors.initials: R
authors.lastname: Schober
authors.forename: Max
authors.initials: M
authors.lastname: Herms
authors.forename: Robert
authors.initials: R
authors.lastname: Grützmann
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schulz
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Stephan
authors.initials: S
authors.lastname: Böhm
authors.forename: Thomas
authors.initials: T
authors.lastname: Berg
authors.forename: Henning
authors.initials: H
authors.lastname: Wittenburg
authors.forename: Joachim
authors.initials: J
authors.lastname: Mössner
authors.forename: Rene
authors.initials: R
authors.lastname: te Morsche
authors.forename: Monique
authors.initials: M
authors.lastname: Derikx
authors.forename: Volker
authors.initials: V
authors.lastname: Keim
authors.forename: Heiko
authors.initials: H
authors.lastname: Witt
authors.forename: Joost P H
authors.initials: JP
authors.lastname: Drenth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D008049:Lipase / Q000235:genetics*; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000235:genetics*; D055815:Young Adult; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent