Moodie Simon J, Ang Liza, Stenner Jonathan M C, Finlayson Caroline, Khotari Archana, Levin Gerald E, Maxwell J Douglas
The Rayne Institute, St Thomas Hospital, London, UK.
Eur J Gastroenterol Hepatol. 2002 Mar;14(3):223-9. doi: 10.1097/00042737-200203000-00004.
To identify the most appropriate testing strategy for genetic haemochromatosis in a liver clinic population by determining the ethnic distribution of the HFE mutations and the relationship between serum iron markers, hepatic siderosis and HFE genotype.
Observational study of 427 patients being investigated for abnormal liver function tests between 1997 and 2000 attending a liver clinic at a teaching district general hospital in south London, UK.
All patients were tested for H63D and C282Y gene mutations, and the ethnic origin was determined. Data were available for most patients for non-fasting serum iron, ferritin and transferrin saturation on presentation and fibrosis and siderosis scores from liver biopsy.
The C282Y mutation was not detected in any patients of Asian or Afro-Caribbean origin but was found almost exclusively in northern Europeans, especially those classified as Celtic, one in seven of whom were heterozygous for this mutation. Three per cent of all the patients tested were C282Y homozygotes. The H63D mutation was distributed more widely. An elevated serum transferrin saturation was both a more sensitive and a more specific test for genetic haemochromatosis than either serum ferritin or iron. Significantly raised mean siderosis scores were found on liver biopsy in C282Y homozygote and C282Y/H63D compound heterozygote groups but not in wild-type, simple heterozygote, or H63D homozygote groups. Forty-five per cent of the C282Y homozygotes detected already had cirrhosis.
In a multiracial liver clinic population, previously undiagnosed C282Y homozygosity was found to be common (3% in our study) but restricted to those of northern European heritage, particularly those with Celtic ancestry. A serum transferrin saturation proved a better initial test to select patients for genotyping than serum iron or ferritin. Laboratory costs can be minimized with no loss of diagnostic sensitivity by selecting patients for genotyping based on northern European ethnic origin and raised serum transferrin saturation.
通过确定HFE基因突变的种族分布以及血清铁标志物、肝铁沉积与HFE基因型之间的关系，确定肝脏门诊人群遗传性血色素沉着症最合适的检测策略。
对1997年至2000年间在英国伦敦南部一家教学区综合医院肝脏门诊接受肝功能异常检查的427例患者进行观察性研究。
对所有患者进行H63D和C282Y基因突变检测，并确定种族来源。大多数患者可获得就诊时非空腹血清铁、铁蛋白和转铁蛋白饱和度数据，以及肝活检的纤维化和铁沉积评分。
在任何亚洲或非洲加勒比裔患者中均未检测到C282Y突变，但几乎仅在北欧人中发现，尤其是那些被归类为凯尔特人的人，其中七分之一为此突变的杂合子。所有检测患者中有3%为C282Y纯合子。H63D突变分布更广泛。血清转铁蛋白饱和度升高对遗传性血色素沉着症的检测比血清铁蛋白或铁更敏感、更特异。在C282Y纯合子和C282Y/H63D复合杂合子组的肝活检中发现平均铁沉积评分显著升高，但在野生型、单纯杂合子或H63D纯合子组中未发现。检测到的C282Y纯合子中有45%已经患有肝硬化。
在一个多种族的肝脏门诊人群中，先前未诊断出的C282Y纯合子很常见（在我们的研究中为3%），但仅限于北欧血统的人，特别是有凯尔特血统的人。血清转铁蛋白饱和度被证明是比血清铁或铁蛋白更好的初步检测方法，用于选择进行基因分型的患者。通过根据北欧种族来源和升高的血清转铁蛋白饱和度选择患者进行基因分型，可将实验室成本降至最低，且不损失诊断敏感性。
