IDENTIFICATION OF SITOSTEROLEMIA LOCUS BY LINKAGE ANALYSES

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Sitosterolemia is a rare lipid disorder characterized by the presence of tendon and tuberous xanthomas, premature atherosclerotic disease, absence of a family history of premature coronary artery disease. Patients suffering form this disease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Identification of this gene defect may therefore throw light on regulation of net dietary cholesterol absorption and lead to advancement in the management of this important cardiovascular risk factor. Therefore, we performed (1) mapping a gene of sitosterolemia locus in subjects with sitosterolemia, and (2) Identification of sitosterolemia gene related products in diabetes mellitus, another common disease that shows plasma high plant sterol levels. By studying 10 well-characterized families with sitosterolemia, we have localized the genetic defect to chromosome 2p21, between microsatellite markers D2S1352. By studying diabetic patients, model animals, and intestinal cell line, we observed that insulin-deficient state leads to the increased intestinal plant sterol absorption, and that this abnormality is related to the intestinal cell growth and differentiation. We are now continuing the further studies on these 2 important themes.