title: Association of myeloperoxidase promotor polymorphism with cirrhosis in patients with hereditary hemochromatosis.
abstract: 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.
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Wien, Austria.
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Osterreicher
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.forename: Felix
authors.initials: F
authors.lastname: Stickel
authors.forename: Claus
authors.initials: C
authors.lastname: Hellerbrand
authors.forename: Melitta
authors.initials: M
authors.lastname: Penz
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
authors.forename: Fritz
authors.initials: F
authors.lastname: Wrba
authors.forename: Edward
authors.initials: E
authors.lastname: Penner
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
mesh_terms: 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
chemical_list: D008565:Membrane Proteins; D009195:Peroxidase; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1