Asberg Arne, Hveem Kristian, Kannelønning Kjell, Irgens Wenche Øiestad
Department of Clinical Chemistry, Trondheim University Hospital, Trondheim, Norway.
Scand J Gastroenterol. 2007 Sep;42(9):1073-7. doi: 10.1080/00365520701245488.
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.
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.
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%.
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.
遗传性血色素沉着症是一种由于体内铁蓄积所致的常见遗传病。大多数病例为HFE基因C282Y突变的纯合子，但只有少数纯合子会罹患临床血色素沉着症。C282Y/C282Y基因型外显率的估计差异很大。本研究的目的是使用严格的定义（即肝硬化）来估计外显率。
将先前对遗传性血色素沉着症进行表型群体筛查的结果与医院数据库中的发现相结合，以估计挪威一个郡有或无肝硬化的C282Y纯合子数量。C282Y/C282Y基因型的外显率估计为患有肝硬化的C282Y纯合子的比例。我们还使用特定年龄累积风险数据计算了预期患有肝硬化的男性C282Y纯合子数量。
男性纯合子中肝硬化的患病率在3.4%至5.0%之间。该数字与肝硬化的累积风险相符，累积风险从35岁时的0.2%增加到65岁时的约10%。在女性纯合子中，肝硬化的患病率为0.3%。
一小部分但数量可观的挪威男性C282Y纯合子如果其血色素沉着症未及时诊断和治疗，将会患上肝硬化。女性的外显率远低于男性。
