Analysis of Locus for Autosomal Dominant Hyperlipidemia

为探讨常染色体显性遗传高脂血症与基因座的关系，对高脂血症患者及其家系成员进行了LDL受体、载脂蛋白B、载脂蛋白E和载脂蛋白AI基因分析。本研究结果表明，家族性高胆固醇血症患者LDL受体基因突变的来源在不同的家族中有很大的差异，对家族成员LDL受体基因的RFLP分析有助于家族性高胆固醇血症的基因诊断。此外，我们的数据表明，常染色体显性高胆固醇血症与肌腱黄瘤遗传分为两组，即，一个由于突变的LDL受体基因和其他由于在该位点的突变，除了LDL受体位点。明确载脂蛋白B基因突变是否导致常染色体显性高胆固醇血症伴肌腱黄色瘤是很重要的。除上述结果外，我们的数据还表明：1）载脂蛋白E4与生活在大城市的日本人的高胆固醇血症有关。2)日本人载脂蛋白AI RFLPs S2等位基因与心肌梗死无关3)家族性混合型高脂血症在日本也很常见。

In order to examine the relationship between autosomal dominant hyperlipidemia and loci, gene for LDL receptor, apolipoprotein B, apolipoprotein E, and apolipoprotein AI were analyzed on hyperlipidemic individuals and their family members. The data obtained in this study indicate that the orgin of mutations of the LDL receptor gene tends to very among defferent families with familial hypercholesterolemia and that the analysis of RFLPs for the LDL receptor gene in family members is useful for the gene diagnosis of familial hypercholesterolemia. In addition, our date indicate that autosomal dominant hypercholesterolemia associated with tendon xanthomas is genetically divided into two groups, that is, the one due to the mutant LDL receptor gene and the other due to mutantions in the locus except the LDL receptor locus. It is important to clarify whether the mutation in the apolipoprotein B gene results in autosomal dominant hypercholesterolemia associated with tendon xanthomas. Besides the results described above, our date also suggest the following: 1) Apolipoprotein E4 is associated with hypercholesterolemia in Japanese living in large cities. 2) S2 allele of apolipoprotein AI RFLPs is not associate with myocardial infarction in Japanese. 3) Familial combined hyperlipidemia is also common in Japanese.