Analysis of genes causing autosomal dominant hypercholesterolemia

点击翻译按钮获取中文摘要

To clarify genetic causes of autosomal dominant hypercholesterolemia, pedigree analysis of genes encoding LDL receptor and apolipoprotein B were performed in families with hereditary hypercholesterolemia. In all 17 families with probands having relatively severe hypercholesterolemia (cholesterol levels 300- 450 mg/dl) associated with Achilles tendon xanthomas, relatively severe . hypercholesterolemia was linked with a partial deletion, an abnormal TaqI band, or RFLP of the LDL receptor gene, indicating that most of, if not all, the relatively severe hypercholesterolemia associated with Achilles tendon xanthomas is caused by a defective LDL receptor gene. On the other hand, only two families seemed to be classic familial hypercholesterolemia in ten families with hereditary hypercholesterolemia which were selected by family studies following school surveys. Moderate hereditary hypercholesterolemia was observed in the remaining eight families. Among the eight families, the LDL receptor gene RFLP was linked with hypercholesterolemia in two families and clinical,features of familial combined hyperlipoproteinemia were observed in another two families. No linkage relationship was observed between LDL receptor gene RFLP and hypercholesterolemia in three of the other four families. The gene for familial defective apolipoprotein B-100 was not detected in these families. These data suggest that moderate hereditary hypercholesterolemia is more common than classic familial hypercholesterolemia and that many of moderate hereditary hypercholesterolemia may be caused by a defective gene at the loci distinct from the LDL receptor gene.