Melis Maria Antonietta, Cau Milena, Deidda Federica, Barella Susanna, Cao Antonio, Galanello Renzo
Dipartimento Scienze Biomediche e Biotecnologie, Sezione Clinica e Biología dell'Età Evolutiva, Università degli Studi di Cagliari, Italy.
Haematologica. 2002 Mar;87(3):242-5.
Hereditary hemochromatosis (HH) is an autosomal recessive disorder of iron metabolism. The HFE gene implicated in this disorder has been identified on chromosome 6 (6p21.3). The most prevalent mutation in HH patients changes the 282 cysteine residue to tyrosine (C282Y). The role of a second mutation which changes the 63 histidine to aspartic acid (H63D) in iron overload has been controversial. The aim of this study was to evaluate the effect of the H63D mutation on the ferritin levels of beta-thalassemia carriers.
beta-thalassemia carriers have a tendency to increase iron absorption because of mild anemia and slightly increased erythropoiesis. Differences in ferritin levels between homozygotes for H63D and wild type may indicate a modulator effect of the HFE mutation on iron absorption. We studied 152 healthy males, heterozygous for beta-thalassemia. Serum ferritin was measured by chemiluminescence. H63D genotypes were determined by digestion of polymerase chain reaction (PCR) products with MboI restriction enzyme.
Forty-five subjects were H63D heterozygotes and four subjects were H63D homozygotes. Ferritin levels were (mean +/- SD): 250 +/- 138 microg/L in homozygotes for the wild type H/H; 295 +/- 186 microg/L in H/D heterozygotes; and 389 +/- 75 microg/L in homozygotes for the mutation D/D. The difference in ferritin values between H/H and D/D is statistically significant (p=0.022).
beta-thalassemia carriers who are homozygotes for the H63D mutation have higher ferritin levels than beta-thalassemia carriers with the H/H genotype, suggesting that the H63D mutation may have a modulating effect on iron absorption.
遗传性血色素沉着症（HH）是一种常染色体隐性铁代谢紊乱疾病。与该疾病相关的HFE基因已在6号染色体（6p21.3）上被确定。HH患者中最常见的突变是将282位的半胱氨酸残基变为酪氨酸（C282Y）。将63位组氨酸变为天冬氨酸（H63D）的第二种突变在铁过载中的作用一直存在争议。本研究的目的是评估H63D突变对β地中海贫血携带者铁蛋白水平的影响。
β地中海贫血携带者因轻度贫血和红细胞生成略有增加而有铁吸收增加的倾向。H63D纯合子与野生型之间铁蛋白水平的差异可能表明HFE突变对铁吸收有调节作用。我们研究了152名健康男性，他们都是β地中海贫血的杂合子。血清铁蛋白通过化学发光法测量。H63D基因型通过用MboI限制酶消化聚合酶链反应（PCR）产物来确定。
45名受试者是H63D杂合子，4名受试者是H63D纯合子。铁蛋白水平（均值±标准差）：野生型H/H纯合子为250±138μg/L；H/D杂合子为295±186μg/L；突变型D/D纯合子为389±75μg/L。H/H与D/D之间铁蛋白值的差异具有统计学意义（p = 0.022）。
H63D突变纯合子的β地中海贫血携带者比H/H基因型的β地中海贫血携带者铁蛋白水平更高，这表明H63D突变可能对铁吸收有调节作用。
