International Study on Gene Abnormalities of GETP and LDL-Receptor

众所周知，高脂血症与动脉粥样硬化的发病有关。脂蛋白受体、载脂蛋白、ilpase和脂质转移蛋白的遗传异常导致脂蛋白代谢的各种紊乱。然而，在人群中，血浆脂蛋白紊乱的显着表型和基因型差异已被注意到。本研究的目的是评估血浆胆固醇酯转移蛋白（CETP）和LDL受体基因突变的人群和地区特征。我们比较了日本人、美国人、欧洲人和韩国人的这些差异。CETP缺陷的分子缺陷目前已鉴定出CETP缺陷的6个突变，包括3个常见缺陷（内含子14剪接缺陷=IN14, D442: G=EX15, G181X=EX6）。在日本，超过50%的CETP缺乏归因于两种常见的突变（in14和ex15）。IN14纯合子的hdl -胆固醇水平大于10mg /dl，而EX15纯合子的hdl -胆固醇水平略低于IN14纯合子。一些杂合子显示正常的hdl -胆固醇值。相比之下，CETP缺乏的频率在美国和欧洲非常低。然而，在居住在西雅图的日裔美国人中，我们可以发现CETP缺乏的受试者（4EX15杂合子和IN14和EX15的复合杂合子）。此外，在德国人群中发现了一种新的突变。在美国和欧洲人群中，CETP活性正常的高脂蛋白血症受试者的脂蛋白模式与CETP缺乏的受试者不同，这表明存在不同病因的高脂蛋白血症。低密度脂蛋白受体缺陷在日本人群中发现了26个低密度脂蛋白受体基因突变。其中，5个是常见的突变，这导致了大约三分之一的日本家族性高胆固醇血症患者。这些突变在日本各地都有发现，在某些特定地区没有发现积累。相比之下，美国和欧洲人群的低密度脂蛋白受体突变与日本报道的不同。因此，为了获得我们对日本人口的人类学起源的知识，可能有必要扩大对亚洲人口的遗传分析。少

It is well known that hyperlipidemia is involved in the pathogenesis of atheroscleroses. Genetic abnormalities in lipoprotein receptors, apoproteins, ilpases and lipid transfer proteins cause a variety of disorders in lipoprotein metabolism. However, marked phenotypical and genotypical differences have been noted in plasma lipoprotein disorders between the populations. The aim of the current study was to eveluate the populational and regional characteristics of mutations in the plasma cholesteryl ester transfer protein (CETP) and LDL receptor gene. We compared these differences between the Japanese, American, European and Korean populations.1.Molecular Defects in CETP DeficiencySo far, 6 mutations have been identified in CETP deficiency, including 3 common defects (intron 14 splicing defect=IN14, D442 : G=EX15, G181X=EX6). In Japan, more then 50% of CETP deficiency was attributed to the two common mutations (IN14&EX15). The HDL-cholesterol level of the IN14 homozygotes was more than 10 … More 0 mg/dl, while that of EX15 homezygotes was slightly lower compared with the IN14 homozygotes. Some heterozygotes showed normal HDL-cholesterol values. In contrast, the frequency of CETP deficiency was very low in the United States and Europe. However, in the Japanese-Americans living in Seattle, we could identify subjects with CETP deficiency (4EX15 heterozygotes and a compound heterozygote of IN14 and EX15). Furthermore, a novel mutation was identified in the German population. In the US and European populations, hyperalphalipoproteinemic subjects with normal CETP activity showed lipoprotein patterns that were distinct from those of CETP-deficient subjects, suggesting the presence of hyperalphalipoproteinemia of different etiologies.2.LDL Receptor DefectsTwenty-six mutations in the LDL receptor gene have been identified in the Japanese population. Among these, 5 were common mutations, which contributed to about one-third of Japanese patients with familial hypercholesterolemia. These mutations were found in the areas all over Japan and no accumulation in some specific areas was noted. In contrast, the LDL receptor mutations in the US and European populations were different from those reported from Japan. Therefore, to gain our knowlegde on the anthropological origin of the Japanese population, it may be necessary to extend genetic analyzes in the Asian populations. Less