title: Sequence analysis of the human tyrosylprotein sulfotransferase-2 gene in subjects with chronic pancreatitis.
abstract: OBJECTIVE
  Human trypsinogens are post-translationally sulfated on Tyr154 by the Golgi resident enzyme tyrosylprotein sulfotransferase-2 (TPST2). Tyrosine sulfation stimulates the autoactivation of human cationic trypsinogen. Because increased trypsinogen autoactivation has been implicated as a pathogenic mechanism in chronic pancreatitis, we hypothesized that genetic variants of TPST2 might alter the risk for the disease.
  
  
  METHODS
  We sequenced the 4 protein-coding exons and the adjacent intronic sequences of TPST2 in 151 subjects with chronic pancreatitis and in 169 healthy controls. The functional effect of TPST2 variants on trypsinogen sulfation was analyzed in transfected HEK 293T cells.
  
  
  RESULTS
  We detected 10 common polymorphic variants, including 6 synonymous variants and 4 intronic variants, with similar frequencies in patients and controls. None of the 8 common haplotypes reconstructed from the frequent variants showed an association with chronic pancreatitis. In addition, we identified 5 rare TPST2 variants, which included 3 synonymous alterations, the c.458G>A (p.R153H) nonsynonymous variant and the c.-9C>T variant in the 5' untranslated region. The p.R153H variant was found in a family with hereditary pancreatitis; however, it did not segregate with the disease. In functional assays, both the p.R153H and c.-9C>T TPST2 variants catalyzed trypsinogen sulfation as well as wild-type TPST2.
  
  
  CONCLUSIONS
  Genetic variants of human TPST2 exert no influence on the risk of chronic pancreatitis.
authors.affiliation: Department of Gastroenterology and Hepatology,University of Leipzig, Leipzig, Germany. jonas.rosendahl@medizin.uni-leipzig.de
authors.forename: Jonas
authors.initials: J
authors.lastname: Rosendahl
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Rónai
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Niels
authors.initials: N
authors.lastname: Teich
authors.forename: Henning
authors.initials: H
authors.lastname: Wittenburg
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Joachim
authors.initials: J
authors.lastname: Mössner
authors.forename: Volker
authors.initials: V
authors.lastname: Keim
authors.forename: Andrew R M
authors.initials: AR
authors.lastname: Bradbury
authors.forename: Miklós
authors.initials: M
authors.lastname: Sahin-Tóth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D050500:Pancreatitis, Chronic / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D015238:Sulfotransferases / Q000235:genetics*; D014362:Trypsinogen / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D014362:Trypsinogen; D015238:Sulfotransferases; C114740:TPST2 protein, human
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