Holmström P, Marmur J, Eggertsen G, Gåfvels M, Stål P
Division of Clinical Chemistry, Department of Medical Laboratory Science and Technology, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Gut. 2002 Nov;51(5):723-30. doi: 10.1136/gut.51.5.723.
The role of the HFE S65C mutation in the development of hepatic iron overload is unknown. The aim of the present study was: (A) to determine the HFE S65C frequency in a Northern European population; and (B) to evaluate whether the presence of the HFE S65C mutation would result in a significant hepatic iron overload.
Biochemical iron parameters and HFE mutation analysis (for the C282Y, H63D, and S65C mutations) were analysed in 250 healthy control subjects and collected retrospectively in 296 patients with suspected iron overload (elevated serum ferritin and/or transferrin saturation). The frequency of patients having at least mild iron overload, and mean serum ferritin and transferrin saturation values were calculated for each HFE genotype. For patients carrying the S65C mutation, clinical data, liver biopsy results, and amount of blood removed at phlebotomy were determined.
The HFE S65C mutation was found in 14 patients and eight controls. In controls, the S65C allele frequency was 1.6%. The S65C allele frequency was enriched in non-C282Y non-H63D chromosomes from patients (4.9%) compared with controls (1.9%) (p<0.05). Serum ferritin was significantly increased in controls carrying the S65C mutation compared with those without HFE mutations. Fifty per cent of controls and relatives having the S65C mutation had elevated serum ferritin levels or transferrin saturation. The number of iron overloaded patients was significantly higher among those having HFE S65C compared with those without any HFE mutation. Half of patients carrying the S65C mutation (7/14) had evidence of mild or moderate hepatic iron overload but no signs of extensive fibrosis in liver biopsies. Screening of relatives revealed one S65C homozygote who had no signs of iron overload. Compound heterozygosity with S65C and C282Y or H63D did not significantly increase the risk of iron overload compared with S65C heterozygosity alone.
The HFE S65C mutation may lead to mild to moderate hepatic iron overload but neither clinically manifest haemochromatosis nor iron associated extensive liver fibrosis was encountered in any of the patients carrying this mutation.
HFE基因S65C突变在肝铁过载发生发展中的作用尚不清楚。本研究的目的是：（A）确定北欧人群中HFE基因S65C突变的频率；（B）评估HFE基因S65C突变的存在是否会导致显著的肝铁过载。
对250名健康对照者进行生化铁参数及HFE基因突变分析（检测C282Y、H63D和S65C突变），并对296例疑似铁过载（血清铁蛋白升高和/或转铁蛋白饱和度升高）患者的数据进行回顾性收集。计算每种HFE基因型至少有轻度铁过载的患者频率以及血清铁蛋白和转铁蛋白饱和度的均值。对于携带S65C突变的患者，确定其临床资料、肝活检结果及放血时的抽血量。
14例患者和8名对照者检测到HFE基因S65C突变。在对照者中，S65C等位基因频率为1.6%。与对照者（1.9%）相比，患者中非C282Y非H63D染色体上的S65C等位基因频率更高（4.9%）（p<0.05）。与无HFE基因突变的对照者相比，携带S65C突变的对照者血清铁蛋白显著升高。携带S65C突变的对照者和亲属中有50%血清铁蛋白水平或转铁蛋白饱和度升高。与无任何HFE基因突变者相比，携带HFE基因S65C突变者中铁过载患者的数量显著更多。携带S65C突变的患者中有一半（7/14）有轻度或中度肝铁过载的证据，但肝活检未显示广泛纤维化迹象。对亲属的筛查发现1例S65C纯合子，无铁过载迹象。与单独的S65C杂合子相比，S65C与C282Y或H63D的复合杂合性并未显著增加铁过载风险。
HFE基因S65C突变可能导致轻度至中度肝铁过载，但携带该突变的患者均未出现临床显性血色素沉着症或与铁相关的广泛肝纤维化。
