Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis
Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis
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DOI：
10.1046/j.1365-2141.2003.04436.x
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发表时间：
2003-07-01
影响因子：
6.5
通讯作者：
Worwood, M
中科院分区：
文献类型：
--
作者：
Carter, K;Bowen, DJ;Worwood, M
在英国，90%的遗传性血色病（HH）患者是HFE C282 Y纯合子，一般人群中每150人中就有一人。然而，只有少数人会发展为临床血色病。缺铁改变铁的积累，但也可能是其他遗传因素。结合珠蛋白（Hp）以三种主要类型（Hp 1-1、Hp 2-1或Hp 2-2）存在并结合游离血浆血红蛋白。在男性中，Hp 2-2已被证明与巨噬细胞铁积累和血清铁蛋白浓度增加有关。此外，Hp 2-2的频率在HH患者中显示出增加。我们通过对265名献血员对照组和173名HFE C282 Y纯合子组进行表型和基因分型，确定了Hp的类型。后一组包括66名献血者缺乏提示血色病的临床特征，没有已知的家族史，和68例临床表现为血色病的患者。Hp 2-2频率在对照组和C282 Y纯合子中没有差异。Hp 2-2不是HH发病的危险因素。为了研究铁积累和触珠蛋白类型之间的关系，我们测定了192名男性，首次献血者，年龄20-40岁，缺乏HFE C282 Y和H63 D的转铁蛋白饱和度和血清铁蛋白浓度。转铁蛋白饱和度和血清铁蛋白浓度不随Hp类型而变化。
In the UK, 90% of patients with hereditary haemochromatosis (HH) are homozygous for HFE C282Y, as are one in 150 people in the general population. However, only a minority of these will develop clinical haemochromatosis. Iron loss modifies iron accumulation but so may other genetic factors. Haptoglobin (Hp) exists as three major types (Hp 1-1, Hp 2-1 or Hp 2-2) and binds free plasma haemoglobin. In men, Hp 2-2 has been shown to be associated with increased macrophage iron accumulation and serum ferritin concentration. Furthermore, the frequency of Hp 2-2 was shown to be increased in patients with HH. We determined Hp types by phenotyping and genotyping 265 blood donor control subjects and 173 subjects who were homozygous for HFE C282Y. The latter group included 66 blood donors lacking clinical features suggestive of haemochromatosis and without a known family history, and 68 patients presenting clinically with haemochromatosis. Hp 2-2 frequencies did not differ in control subjects and C282Y homozygotes. Hp 2-2 was not a risk factor for disease development in HH. To investigate the relationship between iron accumulation and haptoglobin type, we determined transferrin saturation and serum ferritin concentration in 192 male, first-time blood donors aged 20-40 years who lacked both HFE C282Y and H63D. Transferrin saturation and serum ferritin concentrations did not vary with Hp type.