Association of myeloperoxidase promotor polymorphism with cirrhosis in patients with hereditary hemochromatosis.
OBJECTIVE
Hereditary hemochromatosis (HHC) is a disorder of iron metabolism with variable penetrance. Oxidative stress plays a central role in the progression to cirrhosis. Several enzymes involved in the production or degradation of reactive oxidants, like myeloperoxidase (MPO) and heme oxygenase (HO)-1 are influenced by promotor polymorphisms. This study assessed the impact of polymorphisms of the MPO (-463G/A) and the HO-1 promotors of Vienna (GT)n on the evolution of cirrhosis in patients with HHC.


METHODS
One-hundred and fifty-eight C282Y homozygotes without cofactors for fibrosis progression (119 males; mean age: 51.0+/-13.3) were studied. All patients underwent liver biopsy. Hepatic iron content was measured by atom absorption spectrophotometry. MPO polymorphism was assessed by RFLP analysis; HO-1 microsatellite polymorphism by a laser-based semi-automated DNA sequencer.


RESULTS
The MPO genotypes GG, GA, and AA were found in 102 (64.6%), 45 and 11 patients, respectively. The GG-genotype was more common in patients with cirrhosis than in those without (78.7 vs. 55.7%, P=0.003). The distribution of HO-1 genotypes was not different. Logistic regression analysis revealed MPO genotype-GG, serum ferritin, age and male sex as independent predictors for cirrhosis.


CONCLUSIONS
MPO genotype GG is associated with cirrhosis in patients with hereditary hemochromatosis.
Osterreicher
Christoph H
CH
Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Wien, Austria.
Datz
Christian
C
Stickel
Felix
F
Hellerbrand
Claus
C
Penz
Melitta
M
Hofer
Harald
H
Wrba
Fritz
F
Penner
Edward
E
Schuppan
Detlef
D
Ferenci
Peter
P
D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1; D006432:Hemochromatosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D015994:Incidence; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics
D008565:Membrane Proteins; D009195:Peroxidase; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1