Haematological effects of the C282YHFE mutation in homozygous and heterozygous states among subjects of northern and southern European ancestry
Haematological effects of the C282YHFE mutation in homozygous and heterozygous states among subjects of northern and southern European ancestry
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DOI：
10.1046/j.1365-2141.2003.04215.x
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发表时间：
2003-03-01
影响因子：
6.5
通讯作者：
Waalen, J
中科院分区：
文献类型：
--
作者：
Beutler, E;Felitti, V;Waalen, J
HFE基因的C282Y和H63D突变的高频率发生在欧洲人群中，即使纯合子和复合杂合子状态与遗传性血色病相关，这是一种降低健康的疾病。这表明杂合子可能具有选择优势。HFE突变增加了血色病患者的铁吸收，并且杂合子的平均转铁蛋白饱和度和铁蛋白水平轻度增加，表明HFE突变可以防止铁耗竭和缺铁性贫血。在这项23681名白人成年人的研究中，平均转铁蛋白饱和度，血清铁蛋白和血红蛋白水平显着高于携带HFE突变的受试者与野生型相比。按种族分析，平均血红蛋白和平均红细胞体积（MCV）显着较低，在那些与南方与北方欧洲血统。C282Y突变携带者在两个种族组中的平均血红蛋白水平增加。与HFE野生型相比，C282 Y突变女性携带者非贫血性铁缺乏症的患病率显着降低。然而，坦率的缺铁性贫血的患病率没有显着差异基因型。分位数：分位数图显示C282Y突变携带者血红蛋白分布的中间范围有一个小但显著的上移，这与平均血红蛋白水平增加而贫血范围无显著变化一致。
High frequencies of the C282Y and H63D mutations of the HFE gene occur in European populations, even though homozygous and compound heterozygous states are associated with hereditary haemochromatosis, which is a disease that decreases fitness. This suggests that heterozygotes may possess a selective advantage. HFE mutations increase iron absorption in patients with haemochromatosis, and the mean transferrin saturations and ferritin levels are mildly increased in heterozygotes, suggesting that HFE mutations may protect against iron depletion and iron deficiency anaemia. In this study of 23 681 Caucasian adults, mean transferrin saturation, serum ferritin and haemoglobin levels were significantly higher in subjects carrying HFE mutations compared with wild types. Analysed by ethnicity, mean haemoglobin and mean erythrocyte volume (MCV) were significantly lower in those with a southern versus northern European ancestry. C282Y mutation carriers had an increased mean haemoglobin level in both ethnic groups. Prevalence of non-anaemic iron deficiency was significantly lower among female carriers of the C282Y mutation compared with HFE wild types. However, prevalence of frank iron deficiency anaemia did not differ significantly among genotypes. Quantile:quantile plots showed a small but significant upward shift in the mid-range of the haemoglobin distribution among C282Y mutation carriers that was consistent with an increased mean haemoglobin level without significant changes in the anaemic range.