title: Genetic analysis of the glutathione s-transferase genes MGST1, GSTM3, GSTT1, and GSTM1 in patients with hereditary pancreatitis.
abstract: BACKGROUND
  Specific mutations in the cationic trypsinogen gene ( PRSS1) are disease-causing in patients with hereditary pancreatitis, but the genetic background still remains mysterious in about 40% of patients with the disease. It has been suggested that oxidative stress contributes to pancreatic damage. The glutathione s-transferases (GSTs) represent major detoxification enzymes that protect cells from oxidative stress.
  
  
  METHODS
  In the present study we tested whether mutations in the MGST1 and GSTM3 genes or common deletions in the GSTT1 and GSTM1 genes are associated with hereditary pancreatitis. We analyzed the entire coding region of MGST1 and GSTM3 in 30 patients that were tested negative for PRSS1 mutations, and we studied 55 controls. For GSTT1 and GSTM1, we investigated 75 hereditary pancreatitis patients who had been tested negative for PRSS1 mutations, 135 hereditary pancreatitis patients with a PRSS1 mutation, and 183 controls. Patients were further subclassified with regard to age of onset of disease as a marker of severity.
  
  
  RESULTS
  No mutation was found in the MGST1 gene. In the GSTM3 gene, we detected a homozygous 670G > A polymorphism (V224I) with similar frequencies in patients and controls. We found no difference in the frequencies of the GSTT1 and GSTM1 null genotypes between patients and controls, and we detected no differences in age of onset in patients with or without GSTT1 and GSTM1 deletions.
  
  
  CONCLUSIONS
  We conclude that genetic alterations in the MGST1, GSTM3, GSTT1, and GSTM1 genes do not play a dominant role in hereditary pancreatitis.
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Pittsburgh, 571 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15213, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schneider
authors.forename: Sandra
authors.initials: S
authors.lastname: Tögel
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.forename: David C
authors.initials: DC
authors.lastname: Whitcomb
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016366:Open Reading Frames / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D010195:Pancreatitis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D012016:Reference Values; D014357:Trypsin / Q000235:genetics; D014362:Trypsinogen / Q000235:genetics
chemical_list: D005982:Glutathione Transferase; D014357:Trypsin; D014362:Trypsinogen; C413545:glutathione S-transferase T1; C122107:microsomal glutathione S-transferase-I; C483009:GSTM3 protein, human; C489303:PRSS1 protein, human