Iron-overload-related disease in HFE hereditary hemochromatosis
Iron-overload-related disease in HFE hereditary hemochromatosis
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DOI：
10.1056/nejmoa073286
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发表时间：
2008-01-17
影响因子：
158.5
通讯作者：
Gertig, Dorota M.
中科院分区：
文献类型：
--
作者：
Allen, Katrina J.;Gurrin, Lyle C.;Gertig, Dorota M.
工作背景：大多数C282 Y（HFE等位基因，最常与遗传性血色病相关）纯合子患者血清铁蛋白和转铁蛋白饱和度水平升高。与铁超载有关的疾病发展在一些C282 Y纯合子，但程度的风险是有争议的。方法：我们评估了HFE基因突变在31,192人的北方欧洲血统之间的40和69岁的人参加了墨尔本协作队列研究，并随访了平均12年。在随机抽样的1438名受试者分层根据HFE基因型，包括所有203 C282 Y纯合子（其中108名女性和95名男性），我们获得了临床和生化数据，包括两套铁测量12年间隔。与铁超载相关的疾病定义为记录的铁超载和以下一种或多种情况：肝硬化，肝纤维化，肝细胞癌，转氨酶水平升高，医生诊断的症状性血色病，以及第二和第三掌指关节的关节病。C282 Y纯合子患铁超载相关疾病的比例为28.4%（95%置信区间[CI]，18.8至40.2）男性和1.2%（95% CI，0.03至6.5）女性。只有一个非C282 Y纯合子（复合杂合子）记录铁超载相关疾病。男性C282 Y纯合子与血清铁蛋白水平为1000微克每升或以上的更容易报告疲劳，关节炎药物的使用，和肝脏疾病的历史比男性谁有野生型gene.Conclusions：在人谁是纯合子的C282 Y突变，铁超载相关的疾病发展在相当大比例的男性，但在一小部分的女性。
Background: Most persons who are homozygous for C282Y, the HFE allele most commonly asssociated with hereditary hemochromatosis, have elevated levels of serum ferritin and transferrin saturation. Diseases related to iron overload develop in some C282Y homozygotes, but the extent of the risk is controversial.Methods: We assessed HFE mutations in 31,192 persons of northern European descent between the ages of 40 and 69 years who participated in the Melbourne Collaborative Cohort Study and were followed for an average of 12 years. In a random sample of 1438 subjects stratified according to HFE genotype, including all 203 C282Y homozygotes (of whom 108 were women and 95 were men), we obtained clinical and biochemical data, including two sets of iron measurements performed 12 years apart. Disease related to iron overload was defined as documented iron overload and one or more of the following conditions: cirrhosis, liver fibrosis, hepatocellular carcinoma, elevated aminotransferase levels, physician-diagnosed symptomatic hemochromatosis, and arthropathy of the second and third metacarpophalangeal joints.Results: The proportion of C282Y homozygotes with documented iron-overload-related disease was 28.4% (95% confidence interval [CI], 18.8 to 40.2) for men and 1.2% (95% CI, 0.03 to 6.5) for women. Only one non-C282Y homozygote (a compound heterozygote) had documented iron-overload-related disease. Male C282Y homozygotes with a serum ferritin level of 1000 microg per liter or more were more likely to report fatigue, use of arthritis medicine, and a history of liver disease than were men who had the wild-type gene.Conclusions: In persons who are homozygous for the C282Y mutation, iron-overload-related disease developed in a substantial proportion of men but in a small proportion of women.