McLaren C E, McLachlan G J, Halliday J W, Webb S I, Leggett B A, Jazwinska E C, Crawford D H, Gordeuk V R, McLaren G D, Powell L W
Department of Mathematics, Moorhead State University, Minnesota, USA.
Gastroenterology. 1998 Mar;114(3):543-9. doi: 10.1016/s0016-5085(98)70538-4.
BACKGROUND & AIMS: An elevated transferrin saturation is the earliest phenotypic abnormality in hereditary hemochromatosis. Determination of transferrin saturation remains the most useful noninvasive screening test for affected individuals, but there is debate as to the appropriate screening level. The aims of this study were to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals and to evaluate potential transferrin saturation screening levels.
Statistical mixture modeling was applied to data from a survey of asymptomatic Australians to estimate the mean transferrin saturation in hemochromatosis heterozygotes and normal individuals. To evaluate potential transferrin saturation screening levels, modeling results were compared with data from identified hemochromatosis heterozygotes and homozygotes.
After removal of hemochromatosis homozygotes, two populations of transferrin saturation were identified in asymptomatic Australians (P < 0.01). In men, 88.2% of the truncated sample had a lower mean transferrin saturation of 24.1%, whereas 11.8% had an increased mean transferrin saturation of 37.3%. Similar results were found in women. A transferrin saturation threshold of 45% identified 98% of homozygotes without misidentifying any normal individuals.
The results confirm that hemochromatosis heterozygotes form a distinct transferrin saturation subpopulation and support the use of transferrin saturation as an inexpensive screening test for hemochromatosis. In practice, a fasting transferrin saturation of > or = 45% identifies virtually all affected homozygous subjects without necessitating further investigation of unaffected normal individuals.
转铁蛋白饱和度升高是遗传性血色素沉着症最早出现的表型异常。测定转铁蛋白饱和度仍然是对受累个体最有用的非侵入性筛查试验，但对于合适的筛查水平存在争议。本研究的目的是估计血色素沉着症杂合子和正常个体的平均转铁蛋白饱和度，并评估潜在的转铁蛋白饱和度筛查水平。
将统计混合模型应用于对无症状澳大利亚人的一项调查数据，以估计血色素沉着症杂合子和正常个体的平均转铁蛋白饱和度。为了评估潜在的转铁蛋白饱和度筛查水平，将建模结果与已确诊的血色素沉着症杂合子和纯合子的数据进行比较。
去除血色素沉着症纯合子后，在无症状澳大利亚人中确定了两个转铁蛋白饱和度群体（P < 0.01）。在男性中，88.2% 的截短样本平均转铁蛋白饱和度较低，为24.1%，而11.8% 的样本平均转铁蛋白饱和度升高，为37.3%。在女性中也发现了类似结果。转铁蛋白饱和度阈值为45% 时，可识别98% 的纯合子，且不会误认任何正常个体。
结果证实血色素沉着症杂合子形成了一个独特的转铁蛋白饱和度亚群，并支持将转铁蛋白饱和度用作血色素沉着症的廉价筛查试验。在实际应用中，空腹转铁蛋白饱和度≥45% 几乎可以识别所有受影响的纯合子个体，而无需对未受影响的正常个体进行进一步检查。
