Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Aug;80(2):578–581. doi: 10.1172/JCI113107

Intestinal cholesterol absorption efficiency in man is related to apoprotein E phenotype.

Y A Kesäniemi, C Ehnholm, T A Miettinen
PMCID: PMC442272  PMID: 3611358

Abstract

Relationship between the efficiency of cholesterol absorption and apolipoprotein E (apoE) phenotype was studied in a random sample of middle-aged Finnish men. Subjects that were either heterozygous or homozygous for the allele epsilon 2 absorbed less and synthesized more cholesterol than those with the phenotype E4/3 and E4/4, the values for the individuals with the most frequent phenotype E3/3 (56% of the population sample) falling in between. Among the whole study group, the sum of the subscripts of apoE phenotype (e.g., E2/3 = 5) was correlated positively with the fractional absorption of cholesterol (r = 0.40; P less than 0.05) and negatively with the serum level of lathosterol, a cholesterol precursor sterol reflecting the activity of cholesterol synthesis (r = -0.48; P less than 0.01). Thus, apoE polymorphism appears to affect the efficiency of cholesterol absorption and may by this mechanism contribute to the variation in plasma total and low density lipoprotein cholesterol concentration.

Full text

PDF
578

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Angelin B., Raviola C. A., Innerarity T. L., Mahley R. W. Regulation of hepatic lipoprotein receptors in the dog. Rapid regulation of apolipoprotein B,E receptors, but not of apolipoprotein E receptors, by intestinal lipoproteins and bile acids. J Clin Invest. 1983 Apr;71(4):816–831. doi: 10.1172/JCI110835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Assmann G., Schmitz G., Menzel H. J., Schulte H. Apolipoprotein E polymorphism and hyperlipidemia. Clin Chem. 1984 May;30(5):641–643. [PubMed] [Google Scholar]
  3. Basu S. K., Brown M. S., Ho Y. K., Havel R. J., Goldstein J. L. Mouse macrophages synthesize and secrete a protein resembling apolipoprotein E. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7545–7549. doi: 10.1073/pnas.78.12.7545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blue M. L., Williams D. L., Zucker S., Khan S. A., Blum C. B. Apolipoprotein E synthesis in human kidney, adrenal gland, and liver. Proc Natl Acad Sci U S A. 1983 Jan;80(1):283–287. doi: 10.1073/pnas.80.1.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown M. S., Goldstein J. L. Lipoprotein receptors in the liver. Control signals for plasma cholesterol traffic. J Clin Invest. 1983 Sep;72(3):743–747. doi: 10.1172/JCI111044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crouse J. R., Grundy S. M. Evaluation of a continuous isotope feeding method for measurement of cholesterol absorption in man. J Lipid Res. 1978 Nov;19(8):967–971. [PubMed] [Google Scholar]
  7. Driscoll D. M., Getz G. S. Extrahepatic synthesis of apolipoprotein E. J Lipid Res. 1984 Dec 1;25(12):1368–1379. [PubMed] [Google Scholar]
  8. Ehnholm C., Lukka M., Kuusi T., Nikkilä E., Utermann G. Apolipoprotein E polymorphism in the Finnish population: gene frequencies and relation to lipoprotein concentrations. J Lipid Res. 1986 Mar;27(3):227–235. [PubMed] [Google Scholar]
  9. Elshourbagy N. A., Liao W. S., Mahley R. W., Taylor J. M. Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc Natl Acad Sci U S A. 1985 Jan;82(1):203–207. doi: 10.1073/pnas.82.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GRUNDY S. M., AHRENS E. H., Jr, MIETTINEN T. A. QUANTITATIVE ISOLATION AND GAS--LIQUID CHROMATOGRAPHIC ANALYSIS OF TOTAL FECAL BILE ACIDS. J Lipid Res. 1965 Jul;6:397–410. [PubMed] [Google Scholar]
  11. Glomset J. A. The plasma lecithins:cholesterol acyltransferase reaction. J Lipid Res. 1968 Mar;9(2):155–167. [PubMed] [Google Scholar]
  12. Gregg R. E., Zech L. A., Schaefer E. J., Brewer H. B., Jr Type III hyperlipoproteinemia: defective metabolism of an abnormal apolipoprotein E. Science. 1981 Feb 6;211(4482):584–586. doi: 10.1126/science.7455696. [DOI] [PubMed] [Google Scholar]
  13. Gregg R. E., Zech L. A., Schaefer E. J., Stark D., Wilson D., Brewer H. B., Jr Abnormal in vivo metabolism of apolipoprotein E4 in humans. J Clin Invest. 1986 Sep;78(3):815–821. doi: 10.1172/JCI112645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kesäniemi Y. A., Färkkilä M., Kervinen K., Koivisto P., Vuoristo M., Miettinen T. A. Regulation of low-density lipoprotein apolipoprotein B levels. Am Heart J. 1987 Feb;113(2 Pt 2):508–513. doi: 10.1016/0002-8703(87)90622-3. [DOI] [PubMed] [Google Scholar]
  15. Koo C., Innerarity T. L., Mahley R. W. Obligatory role of cholesterol and apolipoprotein E in the formation of large cholesterol-enriched and receptor-active high density lipoproteins. J Biol Chem. 1985 Oct 5;260(22):11934–11943. [PubMed] [Google Scholar]
  16. MIETTINEN T. A., AHRENS E. H., Jr, GRUNDY S. M. QUANTITATIVE ISOLATION AND GAS--LIQUID CHROMATOGRAPHIC ANALYSIS OF TOTAL DIETARY AND FECAL NEUTRAL STEROIDS. J Lipid Res. 1965 Jul;6:411–424. [PubMed] [Google Scholar]
  17. Mahley R. W., Innerarity T. L. Lipoprotein receptors and cholesterol homeostasis. Biochim Biophys Acta. 1983 May 24;737(2):197–222. doi: 10.1016/0304-4157(83)90001-1. [DOI] [PubMed] [Google Scholar]
  18. Miettinen T. A. Cholesterol precursors and their diurnal rhythm in lipoproteins of patients with jejuno-ileal bypass and ileal dysfunction. Metabolism. 1985 May;34(5):425–430. doi: 10.1016/0026-0495(85)90207-0. [DOI] [PubMed] [Google Scholar]
  19. Miettinen T. A. Diurnal variation of cholesterol precursors squalene and methyl sterols in human plasma lipoproteins. J Lipid Res. 1982 Mar;23(3):466–473. [PubMed] [Google Scholar]
  20. Miettinen T. A. Gas-liquid chromatographic determination of fecal neutral sterols using a capillary column. Clin Chim Acta. 1982 Sep 15;124(2):245–248. doi: 10.1016/0009-8981(82)90393-x. [DOI] [PubMed] [Google Scholar]
  21. Palmer R. H., Nichols A. V., Dell R. B., Ramakrishnan R., Lindgren F. T., Gong E. L., Blum C. B., Goodman D. S. Lack of relationship in humans of the parameters of body cholesterol metabolism with plasma levels of subfractions of HDL or LDL, or with apoE isoform phenotype. J Lipid Res. 1986 Jun;27(6):637–644. [PubMed] [Google Scholar]
  22. Rall S. C., Jr, Weisgraber K. H., Mahley R. W. Human apolipoprotein E. The complete amino acid sequence. J Biol Chem. 1982 Apr 25;257(8):4171–4178. [PubMed] [Google Scholar]
  23. Sing C. F., Davignon J. Role of the apolipoprotein E polymorphism in determining normal plasma lipid and lipoprotein variation. Am J Hum Genet. 1985 Mar;37(2):268–285. [PMC free article] [PubMed] [Google Scholar]
  24. Stalenhoef A. F., Malloy M. J., Kane J. P., Havel R. J. Metabolism of apolipoproteins B-48 and B-100 of triglyceride-rich lipoproteins in patients with familial dysbetalipoproteinemia. J Clin Invest. 1986 Sep;78(3):722–728. doi: 10.1172/JCI112632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tilvis R. S., Miettinen T. A. Serum plant sterols and their relation to cholesterol absorption. Am J Clin Nutr. 1986 Jan;43(1):92–97. doi: 10.1093/ajcn/43.1.92. [DOI] [PubMed] [Google Scholar]
  26. Utermann G., Jaeschke M., Menzel J. Familial hyperlipoproteinemia type III: deficiency of a specific apolipoprotein (apo E-III) in the very-low-density lipoproteins. FEBS Lett. 1975 Aug 15;56(2):352–355. doi: 10.1016/0014-5793(75)81125-2. [DOI] [PubMed] [Google Scholar]
  27. Utermann G., Kindermann I., Kaffarnik H., Steinmetz A. Apolipoprotein E phenotypes and hyperlipidemia. Hum Genet. 1984;65(3):232–236. doi: 10.1007/BF00286508. [DOI] [PubMed] [Google Scholar]
  28. Weisgraber K. H., Innerarity T. L., Mahley R. W. Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site. J Biol Chem. 1982 Mar 10;257(5):2518–2521. [PubMed] [Google Scholar]
  29. Zannis V. I., Breslow J. L. Human very low density lipoprotein apolipoprotein E isoprotein polymorphism is explained by genetic variation and posttranslational modification. Biochemistry. 1981 Feb 17;20(4):1033–1041. doi: 10.1021/bi00507a059. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES