Manganese superoxide dismutase dimorphism and iron overload, hepatocellular carcinoma, and death in hepatitis C virus-infected patients.
OBJECTIVE
A genetic dimorphism encodes for either alanine (Ala) or valine (Val) in the mitochondrial targeting sequence of manganese superoxide dismutase (MnSOD), and modulates its mitochondrial import and activity. It has been shown that the presence of at least 1 Ala-encoding allele is more frequent in alcoholic patients with cirrhosis than in controls, and increases the risks of liver iron overload, hepatocellular carcinoma (HCC), and death in these patients. The aim of this study was to assess the influence of the Ala-9Val MnSOD dimorphism on the same parameters and events in hepatitis C virus (HCV)-infected patients.


METHODS
We compared the MnSOD genotypic distributions in 94 control subjects and 165 patients with HCV-related cirrhosis. Patients were included at the time of liver biopsy examination showing cirrhosis, and were followed-up prospectively. The mean time of follow-up evaluation was 85.7 +/- 43.8 months.


RESULTS
The distribution of MnSOD genotypes in HCV-infected patients (25% Val/Val homozygotes, 44% Ala/Val heterozygotes, and 31% Ala/Ala homozygotes) did not differ from the distribution in controls (P = .3). MnSOD genotypes did not influence survival (log-rank test, P = .6; relative risk 1.0; 95% confidence interval, 0.6-1.6) or the risk of HCC occurrence (log-rank test, P = .3; relative risk, 1.1; 95% confidence interval, 0.8-1.6).


CONCLUSIONS
Contrary to previous findings in French alcoholic patients, the Ala-encoding MnSOD allele is represented equally in controls and patients with HCV-related cirrhosis, and it does not significantly influence the risks of liver iron overload, HCC, or death in these patients.
Nahon
Pierre
P
Service d'Hépato-Gastroentérologie, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris, Bondy, France.
Sutton
Angela
A
Pessayre
Dominique
D
Rufat
Pierre
P
Ziol
Marianne
M
Ganne-Carrie
Nathalie
N
Charnaux
Nathalie
N
Trinchet
Jean-Claude
JC
Gattegno
Liliane
L
Beaugrand
Michel
M
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006526:Hepatitis C / Q000235:genetics* / Q000401:mortality*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015994:Incidence; D019190:Iron Overload / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase