The Natural History of Serum Iron Indices for HFE C282Y Homozygosity Associated With Hereditary Hemochromatosis
The Natural History of Serum Iron Indices for HFE C282Y Homozygosity Associated With Hereditary Hemochromatosis
复制标题
DOI：
10.1053/j.gastro.2008.08.056
复制
发表时间：
2008-12-01
期刊：
影响因子：
29.4
通讯作者：
Allen, Katrina J.
中科院分区：
文献类型：
--
作者：
Gurrin, Lyle C.;Osborne, Nicholas J.;Allen, Katrina J.
背景与目的：关于C282Y纯合突变个体血清铁蛋白（SF）和转铁蛋白饱和度（TS）水平的纵向研究很少。我们描述了C282Y纯合子中铁含量升高的发展，随访了12年。方法：从31,192名年龄在40-69岁的基线中，我们确定了203名C282Y纯合子（95名男性），其中116名在基线时测量了SF和空腹TS水平（平均年龄，55岁），86名未经治疗，并在随访时进行了铁测量（平均，12年后）。在多变量正态模型下，从基线SF和TS预测随访时SF超过临床阈值的概率。结果：对于C282Y纯合子，基线时，84%的男性和65%的女性SF升高，37%的男性和3%的女性SF升高至1000 μ g/L。对于基线时SF值为300-1000 μ g/L的男性，随访时进展到SF值为300-1000 μ g/L的预测概率在13% - 35%之间，对于女性，在16% - 22%之间。对于基线SF正常的C282Y纯合子，如果不进行治疗，预计SF发病率< 15%，为1000 μ g/L。结论：大多数C282Y纯合子可能发展到足以使其处于铁负荷相关疾病风险的SF水平，其平均年龄为55岁。在男性中，平均55岁时的TS为95%，增加了SF水平在平均65岁时升高的可能性，但这种影响在女性中不存在，很可能是因为与月经相关的生理性失血。
Background & Aims: There are few longitudinal studies of serum ferritin (SF) and transferrin saturation (TS) levels in individuals homozygous for the C282Y mutation. We characterized the development of elevated iron measures in C282Y homozygotes followed for 12 years. Methods: From 31,192 people aged 40-69 years at baseline, we identified 203 C282Y homozygotes (95 males), of whom 116 had SF and fasting TS levels measured at baseline (mean age, 55 years) and 86 were untreated and had iron measures at follow-up (mean, 12 years later). The probabilities of SF at follow-up exceeding clinical thresholds were predicted from baseline SF and TS under a multivariate normal model. Results: For C282Y homozygotes, at baseline, 84% of males and 65% of females had elevated SF and 37% of males and 3% of females had SF > 1000 mu g/L. For males with SF 300-1000 mu g/L at baseline, the predicted probability of progressing to SF > 1000 mu g/L at follow-up was between 13% and 35% and, for females, between 16% and 22%. For C282Y homozygotes with normal baseline SF, < 15% were predicted to develop SF > 1000 mu g/L if left untreated. Conclusions: The majority of C282Y homozygotes who are likely to develop SF levels sufficient to place them at risk of iron overload-related disease will have done so by mean age 55 years. TS > 95% at mean age 55 years in males increases the likelihood that SF levels will be elevated at mean age 65 years, but this effect is absent in females, most likely because of physiologic blood loss associated with menstruation.