Document Detail


A variant in myeloperoxidase promoter hastens the emergence of hepatocellular carcinoma in patients with HCV-related cirrhosis.
MedLine Citation:
PMID:  21907168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Genetic dimorphisms modulate the activities of several pro- or antioxidant enzymes, including myeloperoxidase (MPO), catalase (CAT), manganese superoxide dismutase (SOD2), and glutathione peroxidase 1 (GPx1). We assessed the role of the G(-463)A-MPO, T(-262)C-CAT, Ala16Val-SOD2, and Pro198Leu-GPx1 variants in modulating HCC development in patients with HCV-induced cirrhosis.
METHODS: Two hundred and five patients with HCV-induced, biopsy-proven cirrhosis but without detectable HCC at inclusion were prospectively followed-up for HCC development. The influence of various genotypes on HCC occurrence was assessed with the Kaplan-Meier method.
RESULTS: During follow-up (103.2±3.4 months), 84 patients (41%) developed HCC, and 66 died. Whereas the Ala16Val-SOD2 or Pro198Leu-GPx1 dimorphisms did not modulate the risk, HCC occurrence was increased in patients with either the homozygous GG-MPO genotype (HR=2.8 [1.7-4.4]; first quartile time to HCC occurrence: 45 vs. 96 months; LogRank <0.0001) or the homozygous CC-CAT genotype (HR=1.74 [1.06-2.82]; first quartile time to HCC occurrence: 55 vs. 96 months; LogRank=0.02). Compared to patients with neither of these two at risk factors, patients with only the CC-CAT genotype had a HR of 2.05 [0.9-4.6] (p=0.08) and patients with only the GG-MPO genotype had a HR of 3.8 [1.5-9.1] (p=0.002), while patients with both risk factors had an HR of 4.8 [2.2-10.4] (p<0.0001). However, only the GG-MPO genotype was independently associated with the HCC risk in multivariate Cox analysis.
CONCLUSIONS: The high activity-associated GG-MPO genotype increases the rate of HCC occurrence in patients with HCV-induced cirrhosis.
Authors:
Pierre Nahon; Angela Sutton; Pierre Rufat; Nathalie Charnaux; Abdellah Mansouri; Richard Moreau; Nathalie Ganne-Carrié; Véronique Grando-Lemaire; Gisèle N'Kontchou; Jean-Claude Trinchet; Dominique Pessayre; Michel Beaugrand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-08
Journal Detail:
Title:  Journal of hepatology     Volume:  56     ISSN:  1600-0641     ISO Abbreviation:  J. Hepatol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-18     Completed Date:  2012-05-24     Revised Date:  2012-08-24    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  426-32     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Affiliation:
Service d'Hépatologie, Hôpital Jean Verdier, AP-HP, Bondy, France. pierre.nahon@jvr.aphp.fr
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Carcinoma, Hepatocellular / enzymology,  etiology*,  genetics
Catalase / genetics
Female
Genetic Variation
Genotype
Glutathione Peroxidase / genetics
Hepatitis C, Chronic / complications*
Humans
Liver Cirrhosis / complications*,  etiology
Liver Neoplasms / enzymology,  etiology*,  genetics
Male
Middle Aged
Peroxidase / genetics*
Polymorphism, Single Nucleotide
Promoter Regions, Genetic*
Risk Factors
Superoxide Dismutase / genetics
Chemical
Reg. No./Substance:
EC 1.11.1.-/glutathione peroxidase GPX1; EC 1.11.1.6/Catalase; EC 1.11.1.7/Peroxidase; EC 1.11.1.9/Glutathione Peroxidase; EC 1.15.1.1/Superoxide Dismutase; EC 1.15.1.1/superoxide dismutase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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