Abstract
Background/Aims: 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 ...
Abstract
Background/Aims: 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-I 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. (C) 2005 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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