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

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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.