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Relationship between lipoprotein abnormalities in childhood and the risk for atherosclerotic coronary heart disease in adulthood(Comparison of the effects of genetic and environmental factors on dyslipidemia between children and adults)

Research Project

Project/Area Number 13470166
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionUniversity of the Ryukyus

Principal Investigator

OHTA Takao  University of the Ryukyus, Department of Pediatrics, Professor, 医学部, 教授 (70185271)

Co-Investigator(Kenkyū-buntansha) SAKU Keijiro  Fukuoka University, Department of Internal Medicine, Professor, 医学部, 教授 (40183371)
OKADA Tomoo  Nihon University, Department of Pediatrics, Associate Professor, 医学部, 講師 (50177052)
ENDO Fumio  Kumamoto University, Department of Pediatrics, Professor, 医学部, 教授 (00176801)
TOGUCHI Suzuka  University of the Ryukyus, Department of Pediatrics, Assistant Professor, 医学部附属病院, 助手 (00347147)
AWATA Hisataka  University of the Ryukyus, Department of clinical laboratory sciences, Professor, 医学部, 教授 (00325862)
田村 俊也  琉球大学, 医学部附属病院, 助手 (70315480)
松浦 稔展  琉球大学, 医学部, 助教授 (00315467)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2003: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
KeywordsLife-style related disease / coronary heart disease / ACAT / Atherosclerosis / LDL size / Small dense LDL / CETP / β-3アドレナリン受容体
Research Abstract

1.Acyl-CoA : cholesterol acyltransferase(ACAT)plays important roles in cellular cholesterol homeostasis.Two isoforms of ACAT have been reported(ACAT-1 and ACAT-2).An ACAT inhibitor was shown to have a lipid-lowering effect.The present study was carried out to clarify the relationship between ACAT-1 gene variants and hyperlipidemia.A missense variant(R526G), and a variant in the 5' untranslated region(-77G-.A) were identified.R526G variant did not affect plasma concentrations of lipids or apolipoproteins in subjects studied. However, among hyperlipidemic subjects, plasma concentrations of HDL-C and apoA-I in subjects with -77G-'A variant were significantly higher than those in subjects without variant.These data suggest that the intracellular PC concentration might modulate plasma HDL concentrations.
2.Small LDL particles are more atherogenic than larger LDL particles.To help prevent atherosclerotic coronary heart diseases(ACHD), it may be useful to understand risk factors during childhood. We evaluated LDL-size and its relation tQ other risk factors for ACHD.LDL-size was measured by gradient gel electrophoresis in 586 children.Pattern B(LDL-size < 25.5 nm)was found in 10.8 % of boys and 4.4 % of girls.Children with pattern B had a higher body mass index (BMI) and insulin resistance, and a more atherogenic lipoprotein profile than those with pattern A (LDL-size> 25.5 nm).BMI, insulin resistance and plasma concentrations of TG, glucose and insulin decreased and plasma concentrations of HDL-C and apoA-I increased as LDL-size increased.HDL-C and insulin in boys, and BMI, HDL-C and apoA-I in girls predicted 22.9 % and 28.1 % of the variability of LDL-size, respectively.Although the contribution Qf these parameters to LDL-size in children was less than that in adults, improvement of these parameters by changes in lifestyle might be important for preventing the development of atherosclerosis, even in children.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Katsuren K: "Effects of a New Single-Nucleotide Polymorphism in the Acyl-CoA : Cholesterol Acyltransferase-2 Gene on Plasma Lipids and Apolipoproteins in Patients with Hyperlipidemia."J Antheroscler Thromb. 44. 32-36 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arashiro R: "Effect of Trp64Arg Mutation of the β3-Adrenergic Receptor Gene and C161T Substitution of the Peroxisome Proliferator Activated Receptor g Gene on Obesity in Japanese Children."Pediatr Int. 45. 135-141 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohta T: "The Influence of the Acyl-CoA : Cholesterol Acyltransferase-1 Gene (-77G/A) Polymorphisms on Plasma Lipid and Apolipoprotein Levels in Normolipidemic and Hyperlipidemic Subjects."Biochim Biophys Acta. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuromori Y: "Familial combined hyperlipidemia (FCHL) in children : the significance of early development of hyperapoB lipoproteinemia, obesity and aging."J Atheroscler Thromb. 9. 314-320 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwata F: "Screening for familial combined hyperlipidemia in children using lipid phenotype."J Atheroscler Thromb. 10. 299-303 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimabukuro T: "Low-density lipoprotein particle size and its regulatry factors in school children"J Clin Endocrinol Metab. (In press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katsuren K, et al.: "Structure of the Human Acyl-CoA : Cholesterol Acyltransferase-2(ACAT-2)Gene and Its Relation to Dyslipidemia."Biochim Biophys Acta. 1531. 230-240 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arashiro R, et al.: "Effect of A Common Mutation(D442G)of The Cholesteryl Ester Transfer Protein Gene On Lipids And Lipoproteins In Children."Pediatr Res. 50. 455-459 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohta T, et al.: "Dyslipidemia in young Japanese children : Its relation to familial hypercholesterolemia and familial combined hyperlipidemia."Pediatr Int. 44. 602-607 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katsuren K, et al.: "Effects of a New Single-Nucleotide Polymorphism in the Acyl-CoA : Cholesterol Acyltransferase-2 Gene on Plasma Lipids and Apolipoproteins in Patients with Hyperlipidemia."J Atheroscier Thromb. 10. 32-36 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arashiro R, et al.: "Effect of Trp64Arg Mutation of the b3-Adrenergic Receptor Gene and C161T Substitution of the Peroxisome Proliferator Activated Receptor g Gene on Obesity in Japanese Children."Pediatr International. 45. 135-141 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukuyama S, et al.: "Analysis of Renal Tubular Electrolyte Transporter Genes in Seven Patients with Hypokalemic Metabolic Alkalosis."Kidney Int. 64. 808-816 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ohta T, et al.: "The Influence of the Acyl-CoA : Cholesterol Acyltransferase-1 Gene(-77G/A)Polymorphisms on Plasma Lipid and Apolipoprotein Levels in Normolipidemic and Hyperlipidemic Subjects."Biochim Biophys Acta. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimabukuro T, et al.: "Low-Density ipoprotein Particle Size and Its Regulatory Factors in School Children."J Clin Endocrinol Metab. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikawa H, et al.: "Pravastatin promote oronary collateral circulation in patients with coronary artery disease."Coronary Artery Disease. 13. 377-381 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miura S, et al.: "In vitro transfer of antisense oligodeoxynucleotides into coronary endothelial cells by ultrasound."Biochem Biophys Res commun. 298. 587-590 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miura S, et al.: "Transfer of antisense oligodeoxynucleotides against endothelin receptors and B into human coronary smooth muscle cells and endothelial cells by apolipoprotein E peptide."Circulation Journal. 66. 1054-1056 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhang B. et al.: "Paraoxonase(Pon 1)Q192R polymorphism and serum Ponl activity in diabetic patients on maintenace hemodialysis."Clinical Nephrology. 60. 257-265 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhang B, et al.: "Evaluation of apolipoprotein A-l kinetics in rabbits in vivo using in situ and exogenous radioiodination methods."Lipids. 38. 209-218 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Zhang B, et al.: "Effect of atorvastatin on total lipid profiles assessed by analytical capillary isotachophoresis."Cardiology. 99. 211-213 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okura Y, et al.: "Angiotensin-converting enzyme insertion/deletion genotype is associated with the activities of plasma coagulation factor VII and X independent of triglyceride metabolism."Coronary Artery Disease. 14. 285-291 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miura S, et al.: "High density lipoprotein-induced angiogenesis requires the activation of Ras/MAP kinase in human coronary artery endothelial cells."Arterioscler Thromb Vase Biol. 23. 802-808 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada T, et al.: "New criteria of normal serum lipid levels in Japanese children : The nationwide study."Pediatrics International. 44. 596-601 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuromori Y, et al.: "Familial combined hyperlipidemia(FCHL)in children : the significance of early development of hyperapoB lipoproteinemia, obesity and aging."J Atheroscler Thromb. 9. 314-320 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwata F, et al.: "Screening for familial combined hyperlipidemia in children using lipid phenotype."J Atheroscler Thromb. 10. 299-303 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Iwata F, et al.: "Body fat ratios in urban Chinese children."Pediatrics International. 45. 190-192 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okada T, et al.: "Relationship of post-heparin hepatic and lipoprotein lipases to high density lipoprotein modulation in obese children."Atherosclerosis. 172. 195-196 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Katsuren K: "Effects of a New Single-Nucleotide Polymorphism in the Acyl-CoA : Cholesterol Acyltransferase-2 Gene on Plasma Lipids and Apolipoproteins in Patients with Hyperlipidemia."J Atheroscler Thromb. 44. 32-36 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arashiro R: "Effect of Trp64Arg Mutation of the β3-Adrenergic Receptor Gene and C161T Substitution of the Peroxisome Proliferator Activated Receptor g Gene on Obesity in Japanese Children."Pediatr Int. 45. 135-141 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohta T: "The Influence of the Acyl-CoA : Cholesterol Acyltransferase-1 Gene (-77G/A) Polymorphisms on Plasma Lipid and Apolipoprotein Levels in Normolipidemic and Hyperlipidemic Subjects."Biochim Biophys Acta. In press. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuromori Y: "Familial combined hyperlipidemia (FCHL) in children : the significance of early development of hyperapoB lipoproteinemia, obesity and aging."J Atheroscler Thromb. 9. 314-320 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Iwata F: "Screening for familial combined hyperlipidemia in children using lipid phenotype."J Atheroscler Thromb. 10. 299-303 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohta T: "Dyslipidemia in Young Japanese Children : Its Relation to Familial Hypercholesterolemia and Familial Combined Hyperlipidemia"Pediatr Int. 44. 602-607 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arashiro R: "Effect of Trp64Arg Mutation of the β3-Adrenergic Receptor Gene arid C161T Substitution of the Peroxisome Proliferator Activated Receptor g Gene on Obesity in Japanese Children"Pediatr Int. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Katsuren K: "Effects of a New Single-Nucleotide Polymorphism in the Acyl-CoA : Cholesterol Acyltransferase-2 Gene on Plasma Lipids and Apolipoptoteins in Patients with Hyperlipidemia"J Atheroscler Thromb. (In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 太田孝男: "原発性高脂血症(家族性高コレステロール血症除く)"小児内科. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Katsuren K.: "Structure of the human acyl-CoA : cholesterol acyltransferase-2 (ACAT-2) gene and its relation to dyslipidemia"Biochimica et Biophysica Acta. 66. 230-240 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Arashiro R.: "Effect of a common mutation (D442G) of the cholesterol ester transfer protein gene on lipid and lipoproteins in children"Pediatric Research. 50. 455-459 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 太田孝男: "小児の高脂血症"臨床と研究. 78. 83-86 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 太田孝男: "HDL機能指標としてのFERHDL"循環器科. 50. 412-416 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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