Meyer T E, Ballot D, Bothwell T H, Green A, Derman D P, Baynes R D, Jenkins T, Jooste P L, du Toit E D, Jacobs P J
J Med Genet. 1987 Jun;24(6):348-56. doi: 10.1136/jmg.24.6.348.
The serum ferritin concentration was used as a screening test to identify the presence of iron overload in 599 Afrikaans subjects (300 males and 299 females) living in the South Western Cape, South Africa. Seventeen of the males with concentrations greater than 400 micrograms/l were reevaluated three and five years later. Serum ferritin concentrations were measured again and further diagnostic procedures were carried out. These included an assessment of alcohol intake and measurements of serum gamma glutamyltransferase, the percentage saturation of transferrin, and HLA-A,-B,-C, and -DR loci typing on the subjects as well as their families. Liver biopsies were performed on some affected subjects. Of the original 16 index subjects, four were diagnosed as homozygous for the HLA linked iron loading gene which is responsible for the clinical disease idiopathic haemochromatosis. Six appeared to be heterozygotes, three were heterozygotes who were also abusing alcohol, and two did not fit into any of the diagnostic groups. The calculated gene frequency was 0.082, with an expected heterozygote frequency of 0.148. The fact that no females were identified in the study suggested that the diagnostic criteria for homozygosity (serum ferritin greater than 400 micrograms/l and % saturation greater than 60%) were set too high. The data were therefore recalculated for the 300 males; when this was done the gene frequency was 0.115 and the heterozygote frequency 0.024. Two subjects were diagnosed as homozygotes in the study of family members and 37 as heterozygotes (33 definite and four probable). Both the homozygotes and nine of the heterozygotes showed mild to moderate disturbances of iron metabolism. There was considerable overlap between the phenotype expression in these nine heterozygotes and the homozygotes, probably as a result of setting the threshold for the serum ferritin concentrations at the relatively high value of 400 microgram/ml. By doing this a small subset of heterozygotes with biochemical abnormalities was identified. The results of the present pilot study suggest a high frequency of the HLA linked iron loading gene in the Afrikaner population of South Western Cape.
血清铁蛋白浓度被用作一项筛查试验，以确定生活在南非西开普省的599名南非白人受试者（300名男性和299名女性）是否存在铁过载。对17名血清铁蛋白浓度高于400微克/升的男性在3年和5年后进行了重新评估。再次测量血清铁蛋白浓度，并进行了进一步的诊断程序。这些程序包括评估酒精摄入量以及测量血清γ-谷氨酰转移酶、转铁蛋白饱和度百分比，对受试者及其家人进行HLA-A、-B、-C和-DR位点分型。对一些受影响的受试者进行了肝活检。在最初的16名索引受试者中，4人被诊断为与HLA连锁的铁负荷基因纯合子，该基因是导致临床疾病特发性血色病的原因。6人似乎是杂合子，3人是同时酗酒的杂合子，2人不符合任何诊断组。计算出的基因频率为0.082，预期杂合子频率为0.148。该研究中未发现女性这一事实表明，纯合子的诊断标准（血清铁蛋白大于400微克/升且饱和度百分比大于60%）设定得过高。因此，对300名男性的数据重新进行了计算；重新计算后，基因频率为0.115，杂合子频率为0.024。在家庭成员研究中，2名受试者被诊断为纯合子，37名被诊断为杂合子（33名确定，4名可能）。纯合子和9名杂合子均表现出轻度至中度的铁代谢紊乱。这9名杂合子和纯合子的表型表达存在相当大的重叠，可能是由于将血清铁蛋白浓度阈值设定在相对较高的400微克/毫升。通过这样做，识别出了一小部分有生化异常的杂合子。本初步研究结果表明，在南非西开普省的南非白人人群中，与HLA连锁的铁负荷基因频率较高。
