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J Grove
a Centre for Liver
Research, University of Newcastle upon Tyne, UK, b Department of Pharmacological Sciences
Correspondence to: Dr C P Day, Department of Medicine, The Medical School, Framlington
Place, Newcastle upon Tyne NE2 4HH, UK. Accepted for publication 18 February 1998 Background Keywords:
alcohol;
liver disease;
haemochromatosis;
haemosiderosis;
iron overload;
polymorphism
Iron
overload is common in the livers of alcoholics and may play a role in
disease pathogenesis. An MHC like gene, HFE,
has recently been identified that is mutated in most patients with
hereditary haemochromatosis (C282Y in 90% and H63D in 45% of the remainder).
AimTo examine the
hypothesis that these mutations determine hepatic iron status in
alcoholics and play a role in predisposition to advanced alcoholic
liver disease.
MethodsThe
HFE gene was genotyped in 257 patients with
alcoholic liver disease and 117 locally matched healthy volunteers. In
addition, iron staining was scored (0-4) on biopsy specimens from
fibrotic/cirrhotic patients with and without
HFE mutations matched for age and sex.
ResultsSome 15.7% of
fibrotic/cirrhotic patients were C282Y heterozygotes compared with
13.7% of controls (p = 0.77). One control and three patients were
C282Y homozygotes. Of chromosomes without the C282Y mutation, 68/442
(15.4%) of patients' chromosomes carried the H63D mutation compared
with 36/216 (16.6%) of control chromosomes (p = 0.91). Significant
(>grade 1) hepatocyte iron staining was seen in 6/23 C282Y
heterozygotes and 4/26 H63D heterozygotes compared with 4/23 controls.
ConclusionsPossession
of a single copy of either of the two HFE
mutations influences neither liver iron content nor the risk of
fibrotic disease in alcoholics.
(GUT 1998;43:262-266)
This article has been cited by other articles:
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  V Boige, L Castera, N de Roux, N Ganne-Carrie, B Ducot, G Pelletier, M Beaugrand, and C Buffet Lack of association between HFE gene mutations and hepatocellular carcinoma in patients with cirrhosis Gut, August 1, 2003; 52(8): 1178 - 1181. [Abstract] [Full Text] [PDF]
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 S.F. Stewart and C.P. Day Liver disorder and the HFE locus QJM, September 1, 2001; 94(9): 453 - 456. [Full Text] [PDF]
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 K. Walsh and G. Alexander Alcoholic liver disease Postgrad. Med. J., May 1, 2000; 76(895): 280 - 286. [Abstract] [Full Text]
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J Grove, A K Daly, M F Bassendine, E Gilvarry, and C P Day Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease Gut, April 1, 2000; 46(4): 540 - 545. [Abstract] [Full Text] [PDF]
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N Ganne-Carrie, C Christidis, C Chastang, M Ziol, F Chapel, F Imbert-Bismut, J-C Trinchet, C Guettier, and M Beaugrand Liver iron is predictive of death in alcoholic cirrhosis: a multivariate study of 229 consecutive patients with alcoholic and/or hepatitis C virus cirrhosis: a prospective follow up study Gut, February 1, 2000; 46(2): 277 - 282. [Abstract] [Full Text] [PDF]
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 B. R. Bacon, J. K. Olynyk, E. M. Brunt, R. S. Britton, and R. K. Wolff HFE Genotype in Patients with Hemochromatosis and Other Liver Diseases Ann Intern Med, June 15, 1999; 130(12): 953 - 962. [Abstract] [Full Text] [PDF]
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