Document Detail

Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis.
MedLine Citation:
PMID:  22666428     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-30
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-05     Completed Date:  2012-10-29     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e37981     Citation Subset:  IM    
Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
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MeSH Terms
Aged, 80 and over
Case-Control Studies
Heme Oxygenase-1 / genetics*
Liver Cirrhosis, Alcoholic / enzymology,  genetics
Middle Aged
Pancreatitis / enzymology*,  genetics*
Polymorphism, Single Nucleotide / genetics
Promoter Regions, Genetic / genetics
Repetitive Sequences, Nucleic Acid / genetics
Sequence Analysis, DNA
Young Adult
Reg. No./Substance:
EC protein, human; EC Oxygenase-1

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