Gan Eng K, Trinder Debbie, Ayonrinde Oyekoya T, Olynyk John K
a School of Medicine & Pharmacology, Fremantle Hospital, PO Box 480, Fremantle 6959, WA, Australia.
b School of Medicine & Pharmacology, Fremantle Hospital, PO Box 480, Fremantle 6959, WA, Australia.
Expert Rev Endocrinol Metab. 2009 May;4(3):225-239. doi: 10.1586/eem.09.9.
Hereditary hemochromatosis due to homozygosity for the C282Y mutation in the HFE gene product is the most common autosomal recessive genetic disorder in populations of northern European descent, where it attains a maximum prevalence of approximately one in 200. Cross-sectional and longitudinal studies have revealed that clinically significant iron-overload disease develops in at least 28% of male and 1% of female HFE C282Y homozygotes. The relatively low clinical penetrance is largely unexplained. Current evidence suggests a limited role for digenic inheritance of mutations in iron homeostasis genes in modifying the penetrance of hemochromatosis. Male gender is a strong genetic factor, promoting expression of clinical disease. Dietary intake of alcohol and noncitrus fruit may also act as important environmental modifiers of penetrance. With genetic analyses becoming simpler to perform, new genetic modifiers of hepatic iron loading and liver fibrogenesis are likely to be forthcoming.
由于HFE基因产物中C282Y突变的纯合性导致的遗传性血色素沉着症是北欧血统人群中最常见的常染色体隐性遗传病，在该人群中其患病率最高可达约二百分之一。横断面研究和纵向研究表明，至少28%的男性和1%的女性HFE C282Y纯合子会发展为具有临床意义的铁过载疾病。相对较低的临床外显率在很大程度上无法解释。目前的证据表明，铁稳态基因突变的双基因遗传在改变血色素沉着症的外显率方面作用有限。男性性别是一个强大的遗传因素，会促进临床疾病的表达。酒精和非柑橘类水果的饮食摄入也可能作为外显率的重要环境调节因素。随着基因分析变得更容易进行，可能会出现肝脏铁负荷和肝纤维化形成的新的基因调节因素。
