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，其特征是血浆中植物甾醇水平升高，尽管胆固醇和植物甾醇结构相似，但在正常受试者中几乎无法吸收。我们报道了一个罕见疾病家族的临床特征，并发现家族成员的强制性杂合子增加了血浆植物固醇水平（J脂质杂志31:881,1990）。家族中有3例患者（纯合子）。1例患者因脊柱黄瘤病压迫而截瘫。该患者是第一个在谷固醇血症中出现神经系统症状的受试者（Ann Neurol 28: 390, 1990）。采用人皮肤成纤维细胞、小鼠巨噬细胞对患者血浆中含有大量植物甾醇的脂蛋白代谢异常进行了研究；J774.1，小鼠腹膜巨噬细胞。在患者低密度脂蛋白（LDL）存在的情况下，与对照LDL相比，在成纤维细胞和J774细胞中，未观察到^<14 b> C油酸盐掺入固醇酯方面的异常发现。与高密度脂蛋白（HDL）孵育后，成纤维细胞和小鼠腹腔巨噬细胞的胆固醇外排减少。然而，由于组织固醇含量与血浆脂蛋白相似，这种罕见疾病的早发动脉粥样硬化的机制不能简单地用HDL的逆向胆固醇转运活性降低来解释。需要进一步的实验来确定导致谷固醇血症患者过早动脉粥样硬化的因素。

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.