title: Mutational analysis of the gene encoding the zymogen granule membrane glycoprotein 2 (GP2) in patients with chronic pancreatitis.
abstract: OBJECTIVE
  Premature activation of pancreatic digestive enzymes is considered as a major factor in the pathogenesis of pancreatitis. Genetic alterations of different pancreatic zymogens or their inhibitors have been associated with chronic pancreatitis (CP).
  
  
  METHODS
  We sequenced all 12 GP2 exons in 380 German CP patients and in 182 German control subjects. In addition, we analyzed exon 3 of GP2 in 803 further CP patients and 1780 controls originating from Germany, the Netherlands, and India by targeted DNA sequencing.
  
  
  RESULTS
  We detected 12 nonsynonymous and 6 synonymous exonic variants. All nonsynonymous changes with exception of c.220C>T (p.R74X) and c.502_503delG (p.G168fsX174) in exon 3 and c.541C>T (p.R181X) in exon 4 were missense mutations and predominantly located in exon 3. All nonsynonymous variants were found in single cases only, with exception of 2 alterations, c.355A>G (p.M119V) and c.409G>A (p. A137T), both located in exon 3. To elucidate the role of these 2 exon 3 variants, we investigated additional patients and controls. The frequency of these variants was similar between patients and controls regardless of ethnic background or cause of CP.
  
  
  CONCLUSIONS
  Our data suggest that GP2 alterations do not alter the risk for the development of CP.
authors: Department of Hepatology and Gastroenterology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Berlin, Germany. heiko.witt@lrz.tum.de
authors: Heiko
authors: H
authors: Witt
authors: Jonas
authors: J
authors: Rosendahl
authors: René H M
authors: RH
authors: te Morsche
authors: Sundaresan
authors: S
authors: Santhosh
authors: Ashok
authors: A
authors: Chacko
authors: Hans-Ulrich
authors: HU
authors: Schulz
authors: Olfert
authors: O
authors: Landt
authors: Niels
authors: N
authors: Teich
authors: Volker
authors: V
authors: Keim
authors: Joachim
authors: J
authors: Mössner
authors: Thomas M
authors: TM
authors: Gress
authors: Johann
authors: J
authors: Ockenga
authors: Hartmut
authors: H
authors: Schmidt
authors: Peter
authors: P
authors: Kovacs
authors: Matthias
authors: M
authors: Blüher
authors: Michael
authors: M
authors: Stumvoll
authors: Andreas
authors: A
authors: Kage
authors: David Alexander
authors: DA
authors: Groneberg
authors: Jan B M J
authors: JB
authors: Jansen
authors: Renate
authors: R
authors: Nickel
authors: Joost P H
authors: JP
authors: Drenth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D058851:GPI-Linked Proteins; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D007194:India; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D009426:Netherlands; D050500:Pancreatitis, Chronic / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
chemical_list: C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins