A degradation-sensitive anionic trypsinogen ( PRSS2 ) variant protects against chronic pancreatitis
Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances...
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| Veröffentlicht in: | Nature genetics 2006-06, Vol.38 (6), p.668-673 |
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| creator | Real, Francisco X Koudova, Monika Le Maréchal, Cédric Ammann, Rudolf W Weiss, Frank Ulrich Pfützer, Roland Löhr, Matthias Berg, Thomas Halangk, Juliane Böck, Wolfgang Galavotti, Roberta Chen, Jian-Min Cavestro, Giulia Martina Truninger, Kaspar Keil, Thomas Güldner, Claudia Wiedenmann, Bertram Bargetzi, Mario Gress, Thomas M Cerny, Milos Friess, Helmut Menzel, Hans-Jürgen Dahm, Stefan Rohde, Klaus Kukor, Zoltán Moral, Pedro Spicak, Julius Bernardova, Jana Witt, Heiko Sahin-Tóth, Miklós Becker, Michael Akar, Nejat Destro-Bisol, Giovanni Ockenga, Johann Kähne, Thilo Férec, Claude Teich, Niels Schulz, Hans-Ulrich Macek, Milan Keim, Volker Witt, Ulrike Luck, Werner Bhatia, Eesh Kage, Andreas Rickards, Olga Halangk, Walter Landt, Olfert Eiberg, Hans Nickel, Renate Jansen, Jan B M J Treiber, Matthias Pignatti, Pier Franco Rosendahl, Jonas Rausova, Eva Simon, Peter Drenth, Joost PH Castellani, Carlo Schmidt, Hartmut Groneberg, David Alexander Spedini, Gabriella Malats, Núria Zarnescu, Narcis Octavian Lerch, Markus M Braun, Markus Szepessy, Edit |
| description | Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 × 10−8). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis. |
| doi_str_mv | 10.1038/ng1797 |
| format | Article |
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Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 × 10−8). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng1797</identifier><identifier>PMID: 16699518</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animal Genetics and Genomics ; Base Sequence ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Causes of ; Chronic Disease ; Chronic illnesses ; DNA Primers ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene expression ; Gene Function ; Genetic aspects ; Genetic variation ; Genetics of eukaryotes. Biological and molecular evolution ; Genètica ; Haplotypes ; Health aspects ; Human Genetics ; Humans ; Hydrolysis ; Inflammatory diseases ; letter ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Medical sciences ; Models, Molecular ; Mutation ; Other diseases. Semiology ; Pancreas ; Pancreatitis ; Physiological aspects ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Tripsina ; Tripsinogen ; Trypsin - chemistry ; Trypsin - genetics ; Trypsin - metabolism ; Trypsinogen ; Trypsinogen - chemistry ; Trypsinogen - genetics ; Trypsinogen - metabolism</subject><ispartof>Nature genetics, 2006-06, Vol.38 (6), p.668-673</ispartof><rights>Springer Nature America, Inc. 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2006</rights><rights>info:eu-repo/semantics/openAccess © Springer Nature Publishing AG. Witt H, Sahin-Tóth M, Landt O, Chen JM, Kähne T, Drenth JP et al. A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis. Nat Genet. 2006 Jun; 38(6): 668-73. <a href="http://dx.doi.org/10.1038/ng1797">http://dx.doi.org/10.1038/ng1797</a></rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c714t-ff9de0c03054e096bbb93fe9890f5e5debfde9cd01e764fbc26644b78b3c69ef3</citedby><cites>FETCH-LOGICAL-c714t-ff9de0c03054e096bbb93fe9890f5e5debfde9cd01e764fbc26644b78b3c69ef3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,2727,26974,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17838240$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16699518$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Real, Francisco X</creatorcontrib><creatorcontrib>Koudova, Monika</creatorcontrib><creatorcontrib>Le Maréchal, Cédric</creatorcontrib><creatorcontrib>Ammann, Rudolf W</creatorcontrib><creatorcontrib>Weiss, Frank Ulrich</creatorcontrib><creatorcontrib>Pfützer, Roland</creatorcontrib><creatorcontrib>Löhr, Matthias</creatorcontrib><creatorcontrib>Berg, Thomas</creatorcontrib><creatorcontrib>Halangk, Juliane</creatorcontrib><creatorcontrib>Böck, Wolfgang</creatorcontrib><creatorcontrib>Galavotti, Roberta</creatorcontrib><creatorcontrib>Chen, Jian-Min</creatorcontrib><creatorcontrib>Cavestro, Giulia Martina</creatorcontrib><creatorcontrib>Truninger, Kaspar</creatorcontrib><creatorcontrib>Keil, Thomas</creatorcontrib><creatorcontrib>Güldner, Claudia</creatorcontrib><creatorcontrib>Wiedenmann, Bertram</creatorcontrib><creatorcontrib>Bargetzi, Mario</creatorcontrib><creatorcontrib>Gress, Thomas M</creatorcontrib><creatorcontrib>Cerny, Milos</creatorcontrib><creatorcontrib>Friess, Helmut</creatorcontrib><creatorcontrib>Menzel, Hans-Jürgen</creatorcontrib><creatorcontrib>Dahm, Stefan</creatorcontrib><creatorcontrib>Rohde, Klaus</creatorcontrib><creatorcontrib>Kukor, Zoltán</creatorcontrib><creatorcontrib>Moral, Pedro</creatorcontrib><creatorcontrib>Spicak, Julius</creatorcontrib><creatorcontrib>Bernardova, Jana</creatorcontrib><creatorcontrib>Witt, Heiko</creatorcontrib><creatorcontrib>Sahin-Tóth, Miklós</creatorcontrib><creatorcontrib>Becker, Michael</creatorcontrib><creatorcontrib>Akar, Nejat</creatorcontrib><creatorcontrib>Destro-Bisol, Giovanni</creatorcontrib><creatorcontrib>Ockenga, Johann</creatorcontrib><creatorcontrib>Kähne, Thilo</creatorcontrib><creatorcontrib>Férec, Claude</creatorcontrib><creatorcontrib>Teich, Niels</creatorcontrib><creatorcontrib>Schulz, Hans-Ulrich</creatorcontrib><creatorcontrib>Macek, Milan</creatorcontrib><creatorcontrib>Keim, Volker</creatorcontrib><creatorcontrib>Witt, Ulrike</creatorcontrib><creatorcontrib>Luck, Werner</creatorcontrib><creatorcontrib>Bhatia, Eesh</creatorcontrib><creatorcontrib>Kage, Andreas</creatorcontrib><creatorcontrib>Rickards, Olga</creatorcontrib><creatorcontrib>Halangk, Walter</creatorcontrib><creatorcontrib>Landt, Olfert</creatorcontrib><creatorcontrib>Eiberg, Hans</creatorcontrib><creatorcontrib>Nickel, Renate</creatorcontrib><creatorcontrib>Jansen, Jan B M J</creatorcontrib><creatorcontrib>Treiber, Matthias</creatorcontrib><creatorcontrib>Pignatti, Pier Franco</creatorcontrib><creatorcontrib>Rosendahl, Jonas</creatorcontrib><creatorcontrib>Rausova, Eva</creatorcontrib><creatorcontrib>Simon, Peter</creatorcontrib><creatorcontrib>Drenth, Joost PH</creatorcontrib><creatorcontrib>Castellani, Carlo</creatorcontrib><creatorcontrib>Schmidt, Hartmut</creatorcontrib><creatorcontrib>Groneberg, David Alexander</creatorcontrib><creatorcontrib>Spedini, Gabriella</creatorcontrib><creatorcontrib>Malats, Núria</creatorcontrib><creatorcontrib>Zarnescu, Narcis Octavian</creatorcontrib><creatorcontrib>Lerch, Markus M</creatorcontrib><creatorcontrib>Braun, Markus</creatorcontrib><creatorcontrib>Szepessy, Edit</creatorcontrib><title>A degradation-sensitive anionic trypsinogen ( PRSS2 ) variant protects against chronic pancreatitis</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 × 10−8). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.</description><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Causes of</subject><subject>Chronic Disease</subject><subject>Chronic illnesses</subject><subject>DNA Primers</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene expression</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Genetic variation</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genètica</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Hydrolysis</subject><subject>Inflammatory diseases</subject><subject>letter</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Models, Molecular</subject><subject>Mutation</subject><subject>Other diseases. Semiology</subject><subject>Pancreas</subject><subject>Pancreatitis</subject><subject>Physiological aspects</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Tripsina</subject><subject>Tripsinogen</subject><subject>Trypsin - chemistry</subject><subject>Trypsin - genetics</subject><subject>Trypsin - metabolism</subject><subject>Trypsinogen</subject><subject>Trypsinogen - chemistry</subject><subject>Trypsinogen - genetics</subject><subject>Trypsinogen - 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degradation-sensitive anionic trypsinogen ( PRSS2 ) variant protects against chronic pancreatitis</title><author>Real, Francisco X ; Koudova, Monika ; Le Maréchal, Cédric ; Ammann, Rudolf W ; Weiss, Frank Ulrich ; Pfützer, Roland ; Löhr, Matthias ; Berg, Thomas ; Halangk, Juliane ; Böck, Wolfgang ; Galavotti, Roberta ; Chen, Jian-Min ; Cavestro, Giulia Martina ; Truninger, Kaspar ; Keil, Thomas ; Güldner, Claudia ; Wiedenmann, Bertram ; Bargetzi, Mario ; Gress, Thomas M ; Cerny, Milos ; Friess, Helmut ; Menzel, Hans-Jürgen ; Dahm, Stefan ; Rohde, Klaus ; Kukor, Zoltán ; Moral, Pedro ; Spicak, Julius ; Bernardova, Jana ; Witt, Heiko ; Sahin-Tóth, Miklós ; Becker, Michael ; Akar, Nejat ; Destro-Bisol, Giovanni ; Ockenga, Johann ; Kähne, Thilo ; Férec, Claude ; Teich, Niels ; Schulz, Hans-Ulrich ; Macek, Milan ; Keim, Volker ; Witt, Ulrike ; Luck, Werner ; Bhatia, Eesh ; Kage, Andreas ; Rickards, Olga ; Halangk, Walter ; Landt, Olfert ; Eiberg, Hans ; Nickel, Renate ; Jansen, Jan B M J ; Treiber, Matthias ; Pignatti, Pier Franco ; Rosendahl, Jonas ; Rausova, Eva ; Simon, Peter ; Drenth, Joost PH ; Castellani, Carlo ; Schmidt, Hartmut ; Groneberg, David Alexander ; Spedini, Gabriella ; Malats, Núria ; Zarnescu, Narcis Octavian ; Lerch, Markus M ; Braun, Markus ; Szepessy, Edit</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c714t-ff9de0c03054e096bbb93fe9890f5e5debfde9cd01e764fbc26644b78b3c69ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Causes of</topic><topic>Chronic Disease</topic><topic>Chronic illnesses</topic><topic>DNA Primers</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene expression</topic><topic>Gene Function</topic><topic>Genetic aspects</topic><topic>Genetic variation</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genètica</topic><topic>Haplotypes</topic><topic>Health aspects</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Hydrolysis</topic><topic>Inflammatory diseases</topic><topic>letter</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Models, Molecular</topic><topic>Mutation</topic><topic>Other diseases. Semiology</topic><topic>Pancreas</topic><topic>Pancreatitis</topic><topic>Physiological aspects</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Tripsina</topic><topic>Tripsinogen</topic><topic>Trypsin - chemistry</topic><topic>Trypsin - genetics</topic><topic>Trypsin - metabolism</topic><topic>Trypsinogen</topic><topic>Trypsinogen - chemistry</topic><topic>Trypsinogen - genetics</topic><topic>Trypsinogen - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Real, Francisco X</creatorcontrib><creatorcontrib>Koudova, Monika</creatorcontrib><creatorcontrib>Le Maréchal, Cédric</creatorcontrib><creatorcontrib>Ammann, Rudolf W</creatorcontrib><creatorcontrib>Weiss, Frank Ulrich</creatorcontrib><creatorcontrib>Pfützer, Roland</creatorcontrib><creatorcontrib>Löhr, Matthias</creatorcontrib><creatorcontrib>Berg, Thomas</creatorcontrib><creatorcontrib>Halangk, Juliane</creatorcontrib><creatorcontrib>Böck, Wolfgang</creatorcontrib><creatorcontrib>Galavotti, Roberta</creatorcontrib><creatorcontrib>Chen, Jian-Min</creatorcontrib><creatorcontrib>Cavestro, Giulia Martina</creatorcontrib><creatorcontrib>Truninger, Kaspar</creatorcontrib><creatorcontrib>Keil, Thomas</creatorcontrib><creatorcontrib>Güldner, Claudia</creatorcontrib><creatorcontrib>Wiedenmann, Bertram</creatorcontrib><creatorcontrib>Bargetzi, Mario</creatorcontrib><creatorcontrib>Gress, Thomas M</creatorcontrib><creatorcontrib>Cerny, Milos</creatorcontrib><creatorcontrib>Friess, Helmut</creatorcontrib><creatorcontrib>Menzel, Hans-Jürgen</creatorcontrib><creatorcontrib>Dahm, Stefan</creatorcontrib><creatorcontrib>Rohde, Klaus</creatorcontrib><creatorcontrib>Kukor, Zoltán</creatorcontrib><creatorcontrib>Moral, Pedro</creatorcontrib><creatorcontrib>Spicak, Julius</creatorcontrib><creatorcontrib>Bernardova, Jana</creatorcontrib><creatorcontrib>Witt, Heiko</creatorcontrib><creatorcontrib>Sahin-Tóth, Miklós</creatorcontrib><creatorcontrib>Becker, Michael</creatorcontrib><creatorcontrib>Akar, Nejat</creatorcontrib><creatorcontrib>Destro-Bisol, Giovanni</creatorcontrib><creatorcontrib>Ockenga, Johann</creatorcontrib><creatorcontrib>Kähne, Thilo</creatorcontrib><creatorcontrib>Férec, Claude</creatorcontrib><creatorcontrib>Teich, Niels</creatorcontrib><creatorcontrib>Schulz, Hans-Ulrich</creatorcontrib><creatorcontrib>Macek, Milan</creatorcontrib><creatorcontrib>Keim, Volker</creatorcontrib><creatorcontrib>Witt, Ulrike</creatorcontrib><creatorcontrib>Luck, Werner</creatorcontrib><creatorcontrib>Bhatia, Eesh</creatorcontrib><creatorcontrib>Kage, Andreas</creatorcontrib><creatorcontrib>Rickards, Olga</creatorcontrib><creatorcontrib>Halangk, Walter</creatorcontrib><creatorcontrib>Landt, Olfert</creatorcontrib><creatorcontrib>Eiberg, Hans</creatorcontrib><creatorcontrib>Nickel, Renate</creatorcontrib><creatorcontrib>Jansen, Jan B M J</creatorcontrib><creatorcontrib>Treiber, Matthias</creatorcontrib><creatorcontrib>Pignatti, Pier Franco</creatorcontrib><creatorcontrib>Rosendahl, Jonas</creatorcontrib><creatorcontrib>Rausova, Eva</creatorcontrib><creatorcontrib>Simon, Peter</creatorcontrib><creatorcontrib>Drenth, Joost PH</creatorcontrib><creatorcontrib>Castellani, Carlo</creatorcontrib><creatorcontrib>Schmidt, Hartmut</creatorcontrib><creatorcontrib>Groneberg, David Alexander</creatorcontrib><creatorcontrib>Spedini, Gabriella</creatorcontrib><creatorcontrib>Malats, Núria</creatorcontrib><creatorcontrib>Zarnescu, Narcis Octavian</creatorcontrib><creatorcontrib>Lerch, Markus M</creatorcontrib><creatorcontrib>Braun, Markus</creatorcontrib><creatorcontrib>Szepessy, Edit</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni 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Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Real, Francisco X</au><au>Koudova, Monika</au><au>Le Maréchal, Cédric</au><au>Ammann, Rudolf W</au><au>Weiss, Frank Ulrich</au><au>Pfützer, Roland</au><au>Löhr, Matthias</au><au>Berg, Thomas</au><au>Halangk, Juliane</au><au>Böck, Wolfgang</au><au>Galavotti, Roberta</au><au>Chen, Jian-Min</au><au>Cavestro, Giulia Martina</au><au>Truninger, Kaspar</au><au>Keil, Thomas</au><au>Güldner, Claudia</au><au>Wiedenmann, Bertram</au><au>Bargetzi, Mario</au><au>Gress, Thomas M</au><au>Cerny, Milos</au><au>Friess, Helmut</au><au>Menzel, Hans-Jürgen</au><au>Dahm, Stefan</au><au>Rohde, Klaus</au><au>Kukor, Zoltán</au><au>Moral, Pedro</au><au>Spicak, Julius</au><au>Bernardova, Jana</au><au>Witt, Heiko</au><au>Sahin-Tóth, Miklós</au><au>Becker, Michael</au><au>Akar, Nejat</au><au>Destro-Bisol, Giovanni</au><au>Ockenga, Johann</au><au>Kähne, Thilo</au><au>Férec, Claude</au><au>Teich, Niels</au><au>Schulz, Hans-Ulrich</au><au>Macek, Milan</au><au>Keim, Volker</au><au>Witt, Ulrike</au><au>Luck, Werner</au><au>Bhatia, Eesh</au><au>Kage, Andreas</au><au>Rickards, Olga</au><au>Halangk, Walter</au><au>Landt, Olfert</au><au>Eiberg, Hans</au><au>Nickel, Renate</au><au>Jansen, Jan B M J</au><au>Treiber, Matthias</au><au>Pignatti, Pier Franco</au><au>Rosendahl, Jonas</au><au>Rausova, Eva</au><au>Simon, Peter</au><au>Drenth, Joost PH</au><au>Castellani, Carlo</au><au>Schmidt, Hartmut</au><au>Groneberg, David Alexander</au><au>Spedini, Gabriella</au><au>Malats, Núria</au><au>Zarnescu, Narcis Octavian</au><au>Lerch, Markus M</au><au>Braun, Markus</au><au>Szepessy, Edit</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A degradation-sensitive anionic trypsinogen ( PRSS2 ) variant protects against chronic pancreatitis</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2006-06-01</date><risdate>2006</risdate><volume>38</volume><issue>6</issue><spage>668</spage><epage>673</epage><pages>668-673</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 × 10−8). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>16699518</pmid><doi>10.1038/ng1797</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2006-06, Vol.38 (6), p.668-673 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2746914 |
| source | MEDLINE; Recercat; Nature Journals Online; Alma/SFX Local Collection |
| subjects | Agriculture Animal Genetics and Genomics Base Sequence Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Causes of Chronic Disease Chronic illnesses DNA Primers Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Gene expression Gene Function Genetic aspects Genetic variation Genetics of eukaryotes. Biological and molecular evolution Genètica Haplotypes Health aspects Human Genetics Humans Hydrolysis Inflammatory diseases letter Liver. Biliary tract. Portal circulation. Exocrine pancreas Medical sciences Models, Molecular Mutation Other diseases. Semiology Pancreas Pancreatitis Physiological aspects Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Tripsina Tripsinogen Trypsin - chemistry Trypsin - genetics Trypsin - metabolism Trypsinogen Trypsinogen - chemistry Trypsinogen - genetics Trypsinogen - metabolism |
| title | A degradation-sensitive anionic trypsinogen ( PRSS2 ) variant protects against chronic pancreatitis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T18%3A02%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20degradation-sensitive%20anionic%20trypsinogen%20(%20PRSS2%20)%20variant%20protects%20against%20chronic%20pancreatitis&rft.jtitle=Nature%20genetics&rft.au=Real,%20Francisco%20X&rft.date=2006-06-01&rft.volume=38&rft.issue=6&rft.spage=668&rft.epage=673&rft.pages=668-673&rft.issn=1061-4036&rft.eissn=1546-1718&rft.coden=NGENEC&rft_id=info:doi/10.1038/ng1797&rft_dat=%3Cgale_pubme%3EA183393683%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222682006&rft_id=info:pmid/16699518&rft_galeid=A183393683&rfr_iscdi=true |