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2002 Fiscal Year Final Research Report Summary

The analysis of reverse cholesterol system in apolipoprotein A-1 deficiency

Research Project

Project/Area Number 13672414
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionThe University of Tokyo

Principal Investigator

TSUKAMOTO Kazuhisa  University, Hospital, Assistant, 医学部附属病院, 助手 (20251233)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Yoshiaki  University, Hospital, Lecturer, 医学部附属病院, 講師 (40172879)
YUMOTO Masato  University, Hospital, Assistant, 医学部附属病院, 助手 (30240170)
Project Period (FY) 2001 – 2002
KeywordsApolipoprotein A-1 / HDL / reverse cholesterol transport / anti-oxidation / paraoxonase / atherosclerosis / Apolipoprotein E / oxidation stress
Research Abstract

We experienced a 69-year-old Japanese woman with severely reduced levels of plasma HDL-cholesterol level (5 mg/dl), caused by apolipoprotein (apo) A-I deficiency. She was not symptomatic for coronary heart disease (CHD) despite the accumulated risks for CHD. Therefore, we analyzed not only the genomic DNA sequence, but also the characters of her lipid profile and the HDL-associated enzymes that are supposed to exert anti-atherogenic properties.
The genomic DNA sequencing of apoA-I identified a cytosine deletion at the third base of codon 184 in the fourth exon, which theoretically led to a frame shift mutation and an early termination at codon 200. However, Western blot analysis did not reveal not only a normal apoA-I protein but also a mutant apoA-I protein. The HDL particles were rich in apoE, and the size of HDL particles rich in apoE was large, suggesting that these HDLs would facilitate cholesterol efflux.
The activity of LCAT was only slightly reduced compared with normal controls despite no apoA-I in the plasma, and the protein levels of CETP was in normal ranges despite that this enzyme is proposed to be associated with HDL. Paraoxonase 1 (PON1) is an enzyme that is associated with HDL and exerts an anti-atherogenic property. It has been proposed that PON1 is stabilized with apoA-I on HDL, however, the PON1 protein distributed exclusively on HDL in our patient, while its stability in both the activity and localization on HDL was reduced. This instability in localization of PON1 protein on HDL might facilitate the delivery of PON1 protein to peripheral tissues through HDL particles, probably contributing to the protection from CHD in this patient.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Noto H., Hashimoto Y., Tsukamoto K.et al.: "Exclusive Association of Paraoxonase 1 with HDL Particles in Apolipoprotein A-I Deficiency"Biochemical & Biophysical Research Communications. 289. 395-401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokota H., Hashimoto Y., Yumoto M., Nakahara K.et al.: "Apolipoprotein A-I deficiency with accumulated risk for CHD but no symptoms of CHD"Atherosclerosis. 162. 399-407 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Noto H. Hashimoto Y. Satoh H. Hara M. Iso-o N. Togo M. Kimura S. Tsukamoto K.: "Exclusive Association of Paraoxonase 1 with HDL Particles in Apolipoprotein A-I Deficiency"Biochemical & Biophysical Research Communications. 289. 395-401 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokota H. Hashimoto Y. Okubo S. Yumoto M. Mashige F. Kawamura M. Kotani K. Usuki Y. Shimada S, Kitamura K. Nakahara K.: "Apolipoprotein A-I deficiency with accumulated risk for CHD but no symptoms ; of CHD"Atherosclerosis. 162. 399-407 (2002)

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

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Published: 2004-04-14  

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