Genetic analyses of heme oxygenase 1 (HMOX1) in different forms of pancreatitis.
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.
Department of Internal Medicine, Neurology and Dermatology, Division of Gastroenterology and Rheumatology, University of Leipzig, Leipzig, Germany.
Sebastian
S
Weis
Moritz
M
Jesinghaus
Peter
P
Kovacs
Dorit
D
Schleinitz
Robert
R
Schober
Claudia
C
Ruffert
Max
M
Herms
Henning
H
Wittenburg
Michael
M
Stumvoll
Matthias
M
Blüher
Robert
R
Grützmann
Hans-Ulrich
HU
Schulz
Volker
V
Keim
Joachim
J
Mössner
Peter
P
Bugert
Heiko
H
Witt
Joost P H
JP
Drenth
Knut
K
Krohn
Jonas
J
Rosendahl
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000201:enzymology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult
C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1