PARK Y.B. Kyungpook National University, 医学部, 助教授
KOSTNER G.M. University of Graz, 医学部, 教授
FUJIMOTO W.Y University of Washington, Medical School, Professor, 医学部, 教授
YAMASHITA Shizuya Osaka University Medical School, Assistant Professor, 医学部, 助手 (60243242)
KOSTNER G.M University of Graz, Medical Schol, Professor, 医学部, 教授
KYUNG Y.B.Park National University, Medical School, Associate Professor
|Budget Amount *help
¥6,300,000 (Direct Cost : ¥6,300,000)
Fiscal Year 1996 : ¥6,300,000 (Direct Cost : ¥6,300,000)
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 Deficiency
So 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
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 Defects
Twenty-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.