| Sequence analysis of the human tyrosylprotein sulfotransferase-2 gene in subjects with chronic pancreatitis. | |
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MedLine Citation:
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PMID: 20460947 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: 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. CONCLUSION: Genetic variants of human TPST2 exert no influence on the risk of chronic pancreatitis. |
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Authors:
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Jonas Rosendahl; Zsolt Rónai; Peter Kovacs; Niels Teich; Henning Wittenburg; Matthias Blüher; Michael Stumvoll; Joachim Mössner; Volker Keim; Andrew R M Bradbury; Miklós Sahin-Tóth |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-05-12 |
Journal Detail:
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Title: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] Volume: 10 ISSN: 1424-3911 ISO Abbreviation: Pancreatology Publication Date: 2010 |
Date Detail:
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Created Date: 2010-06-23 Completed Date: 2010-09-20 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 100966936 Medline TA: Pancreatology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 165-72 Citation Subset: IM |
Copyright Information:
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Copyright 2010 S. Karger AG, Basel. |
Affiliation:
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Department of Gastroenterology and Hepatology,University of Leipzig, Leipzig, Germany. jonas.rosendahl@medizin.uni-leipzig.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Base Sequence Female Humans Male Membrane Proteins / genetics* Middle Aged Pancreatitis, Chronic / enzymology, genetics* Pedigree Polymorphism, Genetic Sulfotransferases / genetics* Trypsinogen / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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AA014544/AA/NIAAA NIH HHS; DK058088/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Proteins; 9002-08-8/Trypsinogen; EC 2.8.2.-/Sulfotransferases; EC 2.8.2.20/TPST2 protein, human |
| Comments/Corrections | |
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