βーシトステロ-ル血症の遺伝的異常と病態に関する研究ーステロ-ル吸収機構の異常部位と異常リポ蛋白代謝の検討ー

谷甾醇血症是一种罕见的遗传性疾病，其特征在于植物甾醇的血浆水平增加，尽管胆固醇和植物甾醇之间的结构相似，但植物甾醇在正常受试者中几乎不被吸收。我们已经报道了这种罕见疾病的一个家族的临床特征，并发现该家族成员的强制性杂合子具有增加的植物甾醇血浆水平（J Lipid Res 31：881，1990）。该家系中有3例患者（纯合子）。1例患者因脊柱黄瘤病压迫脊柱而出现截瘫。该患者是第一个在谷甾醇血症中表现出神经症状的受试者（Ann Neurol 28：390，1990）。使用人皮肤成纤维细胞、鼠巨噬细胞系J774.1和小鼠腹膜巨噬细胞研究了从患者血浆中分离的含有大量植物甾醇的脂蛋白的代谢异常。与<14>对照LDL相比，在存在患者低密度脂蛋白（LDL）的情况下，在成纤维细胞和J774细胞中均未观察到^ C油酸酯掺入甾醇酯的异常发现。当<14>载胆固醇的细胞与高密度脂蛋白（HDL）孵育时，成纤维细胞和小鼠腹腔巨噬细胞的胆固醇流出减少。然而，在这种罕见的疾病中，过早动脉粥样硬化的机制不能简单地用HDL的胆固醇逆向转运活性降低来解释，因为组织固醇含量与血浆脂蛋白的含量相似。进一步的实验是必要的，以确定一个因素（S）归因于过早的动脉粥样硬化谷甾醇血症。

Sitosterolemia is a rare inherited disorder characterized by increased plasma levels of plant sterols, which are hardly absorbed in normal subjects despite of structural similarity between cholestrol and plant sterols. We have reported clinical characteristics of a family of this rare disorder, and found that obligatory heterozygotes of the family members have increased plasma levels of plant sterols (J Lipid Res 31 : 881, 1990) . There three affected patiets (homozygote) in the family. One patient showed paraplegia due to spinal compression by spinal xanthomatosis. This patient is the first subjects who presented neurological symptoms in sitosterolemia (Ann Neurol 28 : 390, 1990) .Metabolic abnormality of lipoproteins which contain large amounts of plant sterols isolated from the patients' plasma was studied using human skin fibroblasts, murine macrophage cell line ; J774.1, and mouse peritoneal macrophages. No abnormal finding was observed in terms of ^<14>C oleate incorporation into sterol esters in both fibroblasts and J774 cells in the presence of patients' low-density lipoproteins (LDL) compared with control LDL. Cholesterol efflux from fibroblasts and mouse peritoneal macrophages was decreased when ^<14>C cholesterol loaded cells were incubated with, D high-density lipoproteins (HDL) . However, mechanism of premature atherosclerosis in this rare disorder could not be explained simply by this decreased reverse cholesterol transport activity of HDL, since tissue sterol contents were similar to that of plasma lipoproteins. Further experiments are necessary to determine a factor (s) attributable to premature atherosclerosis in sitosterolemia.