title: Keratin 8 mutations are not associated with familial, sporadic and alcoholic pancreatitis in a population from the United States.
abstract: OBJECTIVE
  Genetic predispositions play a major role in the development of chronic pancreatitis. Recently, a mutation in the keratin 8 gene (G62C) was reported to be associated with chronic pancreatitis in Italy. We determined whether mutations in the keratin 8 gene are associated with familial, sporadic and alcoholic recurrent acute or chronic pancreatitis in a population from the United States.
  
  
  METHODS
  We investigated the relevant genomic region of the keratin 8 gene in 80 patients with familial pancreatitis without a cationic trypsinogen (PRSS1) gene mutation from 52 different families, 21 patients with familial hereditary pancreatitis and a PRSS1 mutation from 20 different families, 126 patients with sporadic pancreatitis without a PRSS1 mutation, 61 patients with alcoholic pancreatitis and 271 controls by direct DNA sequencing.
  
  
  RESULTS
  We found the heterozygous G62C mutation in n = 3/80 patients (n = 2/52 patients from different families, 3.8%) with familial pancreatitis without PRSS1 mutation and in n = 3/126 patients (2.4%) with sporadic pancreatitis. We detected an adjacent heterozygous I63V mutation in n = 2/80 patients (n = 2/52 patients from different families, 3.8%) with familial pancreatitis without PRSS1 mutation and in n = 1/61 patients (1.6%) with alcoholic pancreatitis. We found the G62C mutation in n = 2/271 controls (0.7%) and the I63V mutation in n = 2/271 controls (0.7%). There were no statistically significant differences in the genotype frequencies between patients and controls (p > 0.05). Screening of additional available family members revealed that these variants did not segregate with the disease phenotype. There was no statistically significant difference in the frequency of these keratin 8 variants between patients with chronic pancreatitis and controls (p > 0.05).
  
  
  CONCLUSIONS
  These keratin 8 variants are not associated with familial, sporadic or alcoholic pancreatitis.
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schneider
authors.forename: Janette
authors.initials: J
authors.lastname: Lamb
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.forename: Anthony
authors.initials: A
authors.lastname: Cuneo
authors.forename: Mary E
authors.initials: ME
authors.lastname: Money
authors.forename: David C
authors.initials: DC
authors.lastname: Whitcomb
mesh_terms: D000328:Adult; D003062:Codon / Q000235:genetics; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D007633:Keratins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010195:Pancreatitis / Q000453:epidemiology / Q000235:genetics*; D019512:Pancreatitis, Alcoholic / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D014357:Trypsin / Q000235:genetics; D014362:Trypsinogen / Q000235:genetics; D014481:United States / Q000453:epidemiology
chemical_list: D003062:Codon; D007633:Keratins; D014362:Trypsinogen; D004247:DNA; C489303:PRSS1 protein, human; D014357:Trypsin