Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis.
Heme oxygenase 1 (HMOX1) is the rate limiting enzyme in heme degradation and a key regulator of inflammatory processes. In animal models the course of pancreatitis was ameliorated by up-regulation of HMOX1 expression. Additionally, carbon monoxide released during heme breakdown inhibited proliferati...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3364204?pdf=render |
| _version_ | 1818470554148012032 |
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| author | Sebastian Weis Moritz Jesinghaus Peter Kovacs Dorit Schleinitz Robert Schober Claudia Ruffert Max Herms Henning Wittenburg Michael Stumvoll Matthias Blüher Robert Grützmann Hans-Ulrich Schulz Volker Keim Joachim Mössner Peter Bugert Heiko Witt Joost P H Drenth Knut Krohn Jonas Rosendahl |
| author_facet | Sebastian Weis Moritz Jesinghaus Peter Kovacs Dorit Schleinitz Robert Schober Claudia Ruffert Max Herms Henning Wittenburg Michael Stumvoll Matthias Blüher Robert Grützmann Hans-Ulrich Schulz Volker Keim Joachim Mössner Peter Bugert Heiko Witt Joost P H Drenth Knut Krohn Jonas Rosendahl |
| author_sort | Sebastian Weis |
| collection | DOAJ |
| description | Heme oxygenase 1 (HMOX1) is the rate limiting enzyme in heme degradation and a key regulator of inflammatory processes. In animal models the course of pancreatitis was ameliorated by up-regulation of HMOX1 expression. Additionally, carbon monoxide released during heme breakdown inhibited proliferation of pancreatic stellate cells and might thereby prevent the development of chronic pancreatitis (CP). Transcription of HMOX1 in humans is influenced by a GT-repeat located in the promoter. As such, HMOX1 variants might be of importance in the pathogenesis of pancreatitis.The GT-repeat and SNP rs2071746 were investigated with fluorescence labelled primers and by melting curve analysis in 285 patients with acute pancreatitis, 208 patients with alcoholic CP, 207 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and in 289 controls, respectively. GT-repeat analysis was extended to a total of 446 alcoholic CP patients. In addition, we performed DNA sequencing in 145 patients with alcoholic CP, 138 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and 151 controls. Exon 3 screening was extended to additional patients and controls.S- and L-alleles of the GT-repeat, genotypes and alleles of SNP rs2071746 and non-synonymous variants detected by sequencing were found with similar frequencies in all groups.Although functional data implicate a potential influence of HMOX1 variants on the pathogenesis of pancreatitis, we did not find any association. As rare non-synonymous HMOX1 variants were found in patients and controls, it is rather unlikely that they will have functional consequences essential for pancreatitis development. |
| first_indexed | 2024-04-13T21:38:52Z |
| format | Article |
| id | doaj.art-1337dc08978348a5a44464b13bd9812d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T21:38:52Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-1337dc08978348a5a44464b13bd9812d2022-12-22T02:28:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3798110.1371/journal.pone.0037981Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis.Sebastian WeisMoritz JesinghausPeter KovacsDorit SchleinitzRobert SchoberClaudia RuffertMax HermsHenning WittenburgMichael StumvollMatthias BlüherRobert GrützmannHans-Ulrich SchulzVolker KeimJoachim MössnerPeter BugertHeiko WittJoost P H DrenthKnut KrohnJonas RosendahlHeme oxygenase 1 (HMOX1) is the rate limiting enzyme in heme degradation and a key regulator of inflammatory processes. In animal models the course of pancreatitis was ameliorated by up-regulation of HMOX1 expression. Additionally, carbon monoxide released during heme breakdown inhibited proliferation of pancreatic stellate cells and might thereby prevent the development of chronic pancreatitis (CP). Transcription of HMOX1 in humans is influenced by a GT-repeat located in the promoter. As such, HMOX1 variants might be of importance in the pathogenesis of pancreatitis.The GT-repeat and SNP rs2071746 were investigated with fluorescence labelled primers and by melting curve analysis in 285 patients with acute pancreatitis, 208 patients with alcoholic CP, 207 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and in 289 controls, respectively. GT-repeat analysis was extended to a total of 446 alcoholic CP patients. In addition, we performed DNA sequencing in 145 patients with alcoholic CP, 138 patients with idiopathic/hereditary CP, 147 patients with alcoholic liver cirrhosis, and 151 controls. Exon 3 screening was extended to additional patients and controls.S- and L-alleles of the GT-repeat, genotypes and alleles of SNP rs2071746 and non-synonymous variants detected by sequencing were found with similar frequencies in all groups.Although functional data implicate a potential influence of HMOX1 variants on the pathogenesis of pancreatitis, we did not find any association. As rare non-synonymous HMOX1 variants were found in patients and controls, it is rather unlikely that they will have functional consequences essential for pancreatitis development.http://europepmc.org/articles/PMC3364204?pdf=render |
| spellingShingle | Sebastian Weis Moritz Jesinghaus Peter Kovacs Dorit Schleinitz Robert Schober Claudia Ruffert Max Herms Henning Wittenburg Michael Stumvoll Matthias Blüher Robert Grützmann Hans-Ulrich Schulz Volker Keim Joachim Mössner Peter Bugert Heiko Witt Joost P H Drenth Knut Krohn Jonas Rosendahl Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis. PLoS ONE |
| title | Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis. |
| title_full | Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis. |
| title_fullStr | Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis. |
| title_full_unstemmed | Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis. |
| title_short | Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis. |
| title_sort | genetic analyses of heme oxygenase 1 hmox1 in different forms of pancreatitis |
| url | http://europepmc.org/articles/PMC3364204?pdf=render |
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