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Correlation of Lipoprotein Abnormalities in Childhood with the Risk for Atherosclerotic Coronary Heart Disease (CAD) in Adulthood (HDL function and polymorphism in HDL related genes)

Research Project

Project/Area Number 09670817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionFaculty of Medicine, University of The Ryukyus (1998)
Kumamoto University (1997)

Principal Investigator

OHTA Takao  Faculty of Medicine, 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, Lecturer, 医学部, 講師 (40183371)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsLpA-I / A-II / Atherosclerosis / LDL size / Small LDL / FERHDL / CETP / リポ蛋白
Research Abstract

1. Small low density lipoprotein (LDL) particles are thought to be more atherogenic than larger LDL particles, although this association may depend on plasma triglyceride (TG) and high density lipoprotein (HDL) levels. To help prevent coronary artery disease (CAD), it may be useful to understand risk factors during childhood and adolescence. In the present study, we evaluated low density lipoprotein particle size (LDL-size) by gradient gel electrophoresis in 70 healthy children (30 boys and 40 girls) along with conventional lipid and lipoprotein parameters which are thought to affect LDL-size. The fractional and molar esterification rates (PER and MER) of cholesterol in plasma and HDL were also determined As expected, plasma levels of TG, HDL-cholesterol (HDL-C) and apoA-I were closely associated with LDL-sizes in both sexes. However, a closer association was found between FER in HDL (FERHDL) and LDL-size. In a stepwise multiple regression analysis, FERHDL alone accounted for 76 % and … More 41 % of the variability in LDL-size in boys and girls, respectively. MER in HDL accounted for additional 4 % and 19 % in boys and girls, respectively. Other parameters, including plasma TG, HDL-C and apoA-I had no significant additional effects. Thus, the determination of FERHDL is useful to predict the particle size of LDL in children.
2. Low plasma E{DL-C is a major risk factor for CAD in adults. In the field of pediatrics, subjects with low plasma HDL-C are often found among obese or dyslipidemic children. However, it is not clear whether low HDL-C in children should be considered a risk factor for CAD.The purpose of this study was to evaluate the risk for CAD in children with low HDL-C by comparing their lipid and apolipoprotein levels and physicochemical characteristics of their HDL with those of age-matched children with normal HDL-C and CAD patients with low HDL-C.Plasma lipids and apolipoproteins were measured in 206 dyslipidemic children (dyslipidemic), 65 obese children (obese), 93 CAD patients with low HDL-C (<40 mg/dL) and 128 children with normal HDL-C.To evaluate the physicochemical characteristics of HDL, molar and fractional esterification rates of cholesterol in plasma (MERplasma and FERplasma) and HDL (MERHDL and FERHDL) were determined in 128 children with normal HDL-C, 71 dyslipidemic, 33 obese and 93 CAD.Compared with controls, children with low HDL-C showed atherogenic profiles of lipid and apolipoprotein levels and physicochemical characteristics of HDL.Therefore, we next examined the differences in lipid and apolipoprotein profiles between children with low HOL-C and CAD patients with low HDL-C.We studied two groups of subjects based on the HDL-C level (Group I : <30 mg/dL, Group II 30l-HDL-C<40mgldL). Compared with CAD, Group I children showed less atherogenic apolipoprotein profiles (lower apoB and higher ratio of apoA-I to apoB). Similar findings were also found in Group II children, but the differences were less prominent than those in Group I children. FERHDL in children with low HDL-C were similar to those in CAD.These findings suggest that the physicochemical characteristics of HbL in children with low HDL-C are similar to those in CAD, but the abnormalities of apoB-containing lipoproteins are milder than those in CAD patients. Thus, if we could prevent further changes in the nature of apoB-containing lipoproteins, children with low HDL-C might not become high risk for CAD in later life.
3.Gene analysis for CETP deficiency was carried out by PCR-RFLP for D442G and Intl4A.DNA was extracted from dried blood spots from dyslipidernic children detected by mass screening. Nutritional analysis was performed by clinical dietitian in Kumamoto University hospital. Gene analysis for CETP was done in 181 dyslipidemic children. Children with Intl4A was not found However, we could find 13 children with heterozygote for D442G mutation. Their plasma levels of HDL-C, apoA-I and apoA-II were similar to those in children with no mutations of CETP gene. These results indicate that CETP deficiency in young children may not affect the plasma concentrations of HDL.Other factor might be required to raise the plasma levels of HDL. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] Ohta T: "Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes Mellitus." Eur J Pediatr. 157. 276-281 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T: "Comparison of children and coronary heart disease patients with low high-density lipoprotein cholesterol levels." Atherosclerosis. 137. 321-328 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T: "Soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 correlate with lipid and apolipoprotein risk factors for coronary artery disease in children." Eur J Pediatr. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K: "Quantity and function of high density lipoproteins as an indicator for coronary atherosclerosis." J Am Coll Cardiol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K: "Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis." Jpn Circ J. 63. 19-24 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K: "In vivo kinetics of human apoA-I variants in rabbits." Eur J Clin Invest. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T, Kakiuchi Y, Kuwahara K, Nagata N, Saku K, Takata K, Matsuda I.: "Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children." J Lipid Res. 38. 139-146 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Adachi N, Migita M, Ohta T, Higashi A, Matsuda I.: "Depressed natural killer (NK) cell activity due to decreased population of NK cell in a vitamin E deficient patients with Shwachman syndrome ; reversible NK cell abnormality by a-tocopherol supplementation." Eur J Pediatr. 156. 444-448 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kawano T, Hakamata H, Ohta T, Ding Yi, Ueda S, and Horiuchi S.: "Inhibitory Effects of HepG2 Cell-derived Apolipoprotein A-I-containing Lipoproteins on Cholesteryl Ester Accumulation in Macrophages." Biochemistry. 36. 9816-9825 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K, Takeda Y, Shirai K, Nii T, Ohta T, Arakawa K.: "Long-term follow-up by coronary angiography in a patients with heterozygous familial hypercholesterolemia : a case report." J Cardiology. 30. 137-142 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K, Zhang B, Ohta T, Arakawa K.: "Troglitazone lowers blood pressure and enhances insulin sensitivity in Watanabe heritable hyperlipidemic rabbits." Am J Hypertension. 10. 1027-1033 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K, Zhang B, Ohta T, Arakawa K.: "Effects of troglitazone on serum lipids, lipoproteins, and hyperinsulinemia in watanabe heritable hyperlipidemic rabbits." Current Therapeutic Research. 58. 876-887 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T, Saku K, Takata K, Nagata N, Kyu Kyu Maung, Matsuda I.: "Fractional esterification rate of cholesterol in high density lipoprotein (HDL) can predict the particle size of low density lipoprotein particle and HDL in patients with coronary heart disease." Atherosclerosis. 135. 205-212 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K, Takeda Y, Nii T, Shirai K, Okabe M, Ohta T, Arakawa K.: "Three-dimentional spiral computed tomography angiography as an alternative imaging modality for a silent dissecting aortic aneurysm." Angiology. 48. 1067-1071 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Liu R, Saku K, Jimi S, Ohta T, Takebayashi S, Arakawa K.: "Mechanism of action of gemfibrozil on HDL metabolism and atherosclerosis in WHHL rabbits." Cardiovascular Drugs and Therapy. 11. 659-668 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T, Nishiyama S, Nakamura T, Saku K, Maung KK, Matsuda I.: "Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes Mellitus." Eur J Pediatr. 157. 276-281 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T, Saku K, Nakamura R, Maung KK, Matsuda I.: "Comparison of children and coronary heart disease patients with low high-density lipoprotein cholesterol levels." Atherosclerosis. 137. 321-328 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ou J, Saku K, Jimi S, Ohta T, Takeda Y, Zhang B, Pownall HJ, Arakawa K.: "Mechanism of action of probucol on cholesteryl ester transfer protein (CETP) mRNA in Chinese Hamster Ovary cell line that had been stably transfected with a human CETP gene." Biochim Biophys Acta. 1393. 153-160 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K, Zhang B, Ohta T, Arakawa K.: "Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis" Jap Circ J. 63. 19-24 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T, Saku K, Takata K, Adachi N.: "Soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 correlate with lipid and apolipoprotein risk factors for coronary artery disease in children." Eur J Pediatr. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K, Zhang B, Ohta T, Liu T.Arakawa K.: "Quantity and function of high density lipoproteins as an indicator for coronary atherosclerosis." J Am Coll Cardiol. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saku K, Eckardstein A, Zhang B, Liu R, Jimi S, Ohta T, Assmann G, Arakawa K.: "In vivo kinetics of human apo-A-I variants in rabbits." Eur J Clin Invest. (accepted).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ohta T: "Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes Mellitus." Eur J Pediatr. 157. 276-281 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohta T: "Comparison of children and coronary heart disease patients with low high-density lipoprotein cholesterol levels." Atherosclerosis. 137. 321-328 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohta T: "Soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 correlate with lipid and apolipoprotein risk factors for coronary artery disease in children." Eur J Pediatr. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Saku K: "Quantity and function of high density lipoproteins as an indicator for coronary atherosclerosis." J Am Coll Cardiol. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Saku K: "Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis." Jpn Circ J. 63. 19-24 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Saku K: "In vivo kinetics of human apoA-I variants in rabbits." Eur J Clin Invest. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohta T: "Fractional esterification rate of cholesterol in high density lipoprotein is correlated with low density lipoprotein particle size in children." J Lipid Res. 38. 139-146 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kawano T: "Inhibitory Effects of HepG2 Cell-derived Apolipoprotein A-I-containing Lipoproteins on Cholesteryl Ester Accumulation in Macrophages." Biochemistry. 36. 9816-9825 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Saku K: "Troglitazone lowers blood pressure and enhances insulin sensitivity in Watanabe heritable" Am J Hypertension. 10. 1027-1033 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohta T: "Fractional esterification rate of cholesterol in high density lipoprotein (HDL) can predict the particle size of low density lipoprotein particle and HDL in patients with coronary heart disease." Atherosclerosis. 135. 205-212 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohta T: "Predominance of large low density lipoprotein particles and lower fractional esterification rate of cholesterol in high density lipoprotein in children with insulin-dependent diabetes Mellitus." Eur J Pediatr. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohta T: "Comparison of children and coronary heart disease patients with low high-density lipoprotein cholesterol levels." Atherosclerosis. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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