Penetrance of the C28Y/C282Y genotype of the HFE gene.
OBJECTIVE
Hereditary hemochromatosis is a common genetic disease caused by accumulation of iron in the body. Most cases are homozygous for the C282Y mutation in the HFE gene, but only a minority of homozygotes will ever suffer from clinical hemochromatosis. Estimates of the penetrance of the C282Y/C282Y genotype vary greatly. The purpose of this study was to estimate the penetrance using a stringent definition, i.e. liver cirrhosis.


METHODS
The results from previous phenotypic population screening for hereditary hemochromatosis were combined with findings in hospital databases in order to estimate the number of C282Y homozygotes with and without liver cirrhosis in a Norwegian county. The penetrance of the C282Y/C282Y genotype was estimated as the fraction of C282Y homozygotes with liver cirrhosis. We also calculated the expected number of male C282Y homozygotes with liver cirrhosis using figures for age-specific accumulated risk.


RESULTS
The prevalence of liver cirrhosis in male homozygotes is between 3.4% and 5.0%. This figure is compatible with an accumulated risk of liver cirrhosis that increases from 0.2% at 35 years to about 10% at 65 years of age. In female homozygotes, the prevalence of liver cirrhosis is 0.3%.


CONCLUSIONS
A small but significant number of Norwegian male C282Y homozygotes will contract liver cirrhosis if their hemochromatosis is not diagnosed and treated in time. The penetrance is much lower in women than in men.
Asberg
Arne
A
Department of Clinical Chemistry, Trondheim University Hospital, Trondheim, Norway. arne.asberg@stolav.no
Hveem
Kristian
K
Kannelønning
Kjell
K
Irgens
Wenche Øiestad
WØ
D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008403:Mass Screening; D008499:Medical Records / Q000706:statistics & numerical data; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009664:Norway; D019683:Penetrance; D015995:Prevalence; D012737:Sex Factors
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins