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1996 Fiscal Year Final Research Report Summary

International Study on Gene Abnormalities of GETP and LDL-Receptor

Research Project

Project/Area Number 08044280
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionOsaka University

Principal Investigator

MATSUZAWA Yuji  Osaka University Medical School, Professor, 医学部, 教授 (70116101)

Co-Investigator(Kenkyū-buntansha) PARK Y.B.  Kyungpook National University, 医学部, 助教授
KOSTNER G.M  University of Graz, Medical Schol, Professor, 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)
KYUNG Y.B.Park  National University, Medical School, Associate Professor
Project Period (FY) 1996
KeywordsCETP / CETP Deficiency / Hyperalphalipoproteinemia / LDL-receptor / Familial Hypercholesterolemia / Atherosclerosis
Research Abstract

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 … 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 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. Less

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] S.Yamashita: "Molecular disorders of cholesteryl ester transfer protein" J.Atheroscler Thromb.3(1). 1-11 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Funahashi: "A compound heterozygote for familial hypercholesterolomia with a homozygous mother." J.Intern. Med.239. 187-190 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Nozaki: "The effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolemia: a comparison of morning and evening administration." Eru.J.Clin.Pharmacol.49. 361-364 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N.Sakai: "Exon 10 skipping caused by intron 10 splice donor site mutation in cholesteryl ester transfer protein gene results in abnormal downstream splice site selection." J.Lipid.Res.37. 2065-2073 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Hirano: "Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48." J.Biol.Chem.271. 9887-9890 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Arai: "A novel nonsense mutation (G181X) in the human cholesteryl ester transfer protein gene in Japanese hyperalpherlipoproteinemic subject." J.Lipid.Res.37. 2145-2154 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] W.Chen,: "Genetic analysis on a Japanese cerebrotendinous xanthomatosis family: identification of new mutation in adrenodoxin binding site of CYP27 gene." Biochim. Biophys. Acta.1317. 119-126 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Yamashita: "Molecular genetics of plasma cholesteryl ester transfer protein (CETP)" Current Opinion in Lipidology. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Hirano: "Genetic cholesteryl ester transfer protein deficiency extremely accumulate in Omagari area of Japan." Arterioscler. Thromb. Vasc. Biol.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Yamashita, T.Arai, K.Hirano, N.Sakai, M.Ishigami, N.Nakajima, Y.Matsuzawa: "Molecular disorders of cholesteryl ester tansfer protein" J.Atheroscler Thromb.3 (1). 1-11 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Funahashi, S.Yamashita, T.Maruyama, Y.Ueyama, M.Menju, Y.Nagai, K.Takemura, Y.Miyake, S.Tajima, Y.Matsuzawa: "A compound heterozygote for familial hypercholesterolemia with a homozygous mother." J.Intern.Med.239. 187-190 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Nozaki, T.Nakagwa, A.Nakata, S.Yamashita, K.Kameda-Takemura, T.Nakamura, T.Nakamura, Y.Keno, K.Tokunaga, Y.Matsuzawa: "The effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolemia : a comparison of morning and evening administration." Eur.J.Clin.Pharmacol.49. 361-364 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Sakai, S.Santamarina-Fojo, S.Yamashita, Y.Matsuzawa, H.B.Brewwer, Jr.: "Exon 10 skipping caused by intron 10 splice donor site mutation in cholesteryl ester transfer protein gene results in abnormal downstream splice site selection." J.Lipid.Res.37. 2065-2073 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirano, S.G.Young, R.V.Farese, J.Ng, E.Sande, C.Warburton, L.M.Powell-Braxton, N.O.Davidson: "Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48" J.Biol.Chem.271. 9887-9890 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Arai, S.Yamashita, N.Sakai, K.Hirano, S.Okada, M.Ishigami, H.Kobayashi, S.Nozaki, T.Funahashi, K.Kameda-Takemura, N.Nakajima, Y.Matsuzawa: "A novel nonsense mutation (G181X) in the human cholesteryl ester transfer protein gene in Japanese hyperalpherlipoproteinemic subiject-A common defect affecting plasma high density lipoprotein concentration-" J.Lipid.Res.37. 2145-2154 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] W.Chen, S.Kubota, Y.Nishiura, S.Nozaki, Y.Matsuzawa, S.Yamashita, T.Nakagawa, K.Kameda-Takemura, M.Menju, Bjorkhen, G.Eggertsen, Y.Seyama: "Genetic analysis on a Japanese cerebrotendinous xanthomatosis family : identification of new mutation in adrenodoxin binding site of CYP27 gene." Biochim.Biophys.Acta.1317. 119-126 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Yamashita, N.Sakai, K.Hirano, T.Arai, M.Ishigami, T.Maruyama, Y.Masuzawa: "Molecular genetics of plasma cholesteryl ester transfer rotein (CETP)." Current Opinion in Lipidology. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Hirano, S.Yamashita, N.Nakajima, Y.Yoshida, T.Arai, N.Sakai, M.Ishigami, K.Takemura, Y.Matsuzawa: "Genetic cholesteryl ester transfer protein deficiency extremely accumulate in Omagari area of Japan. -Marked hyperalphalipoproteinemia caused by cholesteryl ester transfer protein gene mutation is not a longevity syndrome.-" Arterioscler.Thromb. Vasc.Biol.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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