title: Genetic background is different between sentinel and recurrent acute pancreatitis.
abstract: OBJECTIVE
  Previous studies have shown an association of variants in trypsin-associated genes, such as cationic trypsinogen (PRSS1) and serine protease inhibitor, Kazal type-1 (SPINK1) with pancreatitis. However, whether these genetic variants are associated with acute pancreatitis (AP) remains largely unknown, especially when the first attack is separated from recurrent attacks.
  
  
  METHODS
  A total of 261 patients with AP (174 with a sentinel attack, and 87 with recurrent attacks) and healthy controls were genotyped for the p.R122H mutation in the PRSS1 gene, p.N34S and IVS3 + 2T > C variants in the SPINK1 gene, the p.G191R variant in the anionic trypsinogen gene, the p.E32del variant in the mesotrypsinogen (PRSS3) gene, and the -2518G > A variant in the monocyte chemoattractant protein-1 gene by polymerase chain reaction-restriction enzyme digestion and direct sequencing.
  
  
  RESULTS
  Patients with recurrent attacks were younger. The proportions of biliary pancreatitis and severe cases were lower, and that of idiopathic pancreatitis was higher in patients with a sentinel attack than in those with recurrent attacks. The frequencies of the genetic variants examined did not differ between controls and patients with sentinel pancreatitis. The frequencies of the PRSS1 p.R122H mutation, SPINK1 p.N34S variant, and PRSS3 p.E32del variant, but not other genetic variants, were higher in patients with recurrent attacks than in controls or those with a sentinel attack.
  
  
  CONCLUSIONS
  The PRSS1 p.R122H mutation, SPINK1 p.N34S, and PRSS3 p.E32del variants were associated with recurrent, but not sentinel AP. The genetic background could possibly be different between sentinel and recurrent AP.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan. amasamune@med.tohoku.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ariga
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kume
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kakuta
authors.forename: Kennichi
authors.initials: K
authors.lastname: Satoh
authors.forename: Akihiko
authors.initials: A
authors.lastname: Satoh
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics*; D010641:Phenotype; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D014357:Trypsin / Q000235:genetics*; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen / Q000235:genetics; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D002352:Carrier Proteins; D018932:Chemokine CCL2; C486642:SPINK1 protein, human; C064831:PRSS2 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; C489303:PRSS1 protein, human; C040749:PRSS3 protein, human; D014357:Trypsin