Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1989 Jan;83(1):137–142. doi: 10.1172/JCI113849

Changes of genetic apolipoprotein phenotypes caused by liver transplantation. Implications for apolipoprotein synthesis.

H G Kraft 1, H J Menzel 1, F Hoppichler 1, W Vogel 1, G Utermann 1
PMCID: PMC303653  PMID: 2521341

Abstract

Liver transplantation provides a unique opportunity to investigate the contribution in vivo of the liver to the synthesis and degradation of genetically polymorphic plasma proteins. We have determined the genetic polymorphisms plasma proteins. We have determined the genetic polymorphisms of apo A-IV, apo E, and of the Lp(a) glycoprotein (apo (a] in the plasma of subjects undergoing liver transplantation and in respective organ donors. The results show that in humans, greater than 90% of the plasma apo E and virtually all apo (a) are liver derived, whereas this organ does not significantly contribute to plasma apo A-IV levels.

Full text

PDF
137

Images in this article

139Image
on p.139
139Image
on p.139
140Image
on p.140

Selected References

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

  1. BERG K. A NEW SERUM TYPE SYSTEM IN MAN--THE LP SYSTEM. Acta Pathol Microbiol Scand. 1963;59:369–382. doi: 10.1111/j.1699-0463.1963.tb01808.x. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Bersot T. P., Innerarity T. L., Pitas R. E., Rall S. C., Jr, Weisgraber K. H., Mahley R. W. Fat feeding in humans induces lipoproteins of density less than 1.006 that are enriched in apolipoprotein [a] and that cause lipid accumulation in macrophages. J Clin Invest. 1986 Feb;77(2):622–630. doi: 10.1172/JCI112345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bilheimer D. W., Goldstein J. L., Grundy S. M., Starzl T. E., Brown M. S. Liver transplantation to provide low-density-lipoprotein receptors and lower plasma cholesterol in a child with homozygous familial hypercholesterolemia. N Engl J Med. 1984 Dec 27;311(26):1658–1664. doi: 10.1056/NEJM198412273112603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Dolphin P. J. Lipoprotein metabolism and the role of apolipoproteins as metabolic programmers. Can J Biochem Cell Biol. 1985 Aug;63(8):850–869. doi: 10.1139/o85-107. [DOI] [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. Dzik W. H., Arkin C. F., Jenkins R. L. Transfer of congenital factor XI deficiency from a donor to a recipient by liver transplantation. N Engl J Med. 1987 May 7;316(19):1217–1218. [PubMed] [Google Scholar]
  9. Eaton D. L., Fless G. M., Kohr W. J., McLean J. W., Xu Q. T., Miller C. G., Lawn R. M., Scanu A. M. Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc Natl Acad Sci U S A. 1987 May;84(10):3224–3228. doi: 10.1073/pnas.84.10.3224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Elshourbagy N. A., Walker D. W., Boguski M. S., Gordon J. I., Taylor J. M. The nucleotide and derived amino acid sequence of human apolipoprotein A-IV mRNA and the close linkage of its gene to the genes of apolipoproteins A-I and C-III. J Biol Chem. 1986 Feb 15;261(5):1998–2002. [PubMed] [Google Scholar]
  12. Fless G. M., Rolih C. A., Scanu A. M. Heterogeneity of human plasma lipoprotein (a). Isolation and characterization of the lipoprotein subspecies and their apoproteins. J Biol Chem. 1984 Sep 25;259(18):11470–11478. [PubMed] [Google Scholar]
  13. Gaubatz J. W., Heideman C., Gotto A. M., Jr, Morrisett J. D., Dahlen G. H. Human plasma lipoprotein [a]. Structural properties. J Biol Chem. 1983 Apr 10;258(7):4582–4589. [PubMed] [Google Scholar]
  14. Ghiselli G., Krishnan S., Beigel Y., Gotto A. M., Jr Plasma metabolism of apolipoprotein A-IV in humans. J Lipid Res. 1986 Aug;27(8):813–827. [PubMed] [Google Scholar]
  15. Green P. H., Glickman R. M. Intestinal lipoprotein metabolism. J Lipid Res. 1981 Nov;22(8):1153–1173. [PubMed] [Google Scholar]
  16. 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]
  17. Havel R. J. George Lyman Duff memorial lecture. Role of the liver in atherosclerosis. Arteriosclerosis. 1985 Nov-Dec;5(6):569–580. doi: 10.1161/01.atv.5.6.569. [DOI] [PubMed] [Google Scholar]
  18. Kamboh M. I., Ferrell R. E. Genetic studies of human apolipoproteins. I. Polymorphism of apolipoprotein A-IV. Am J Hum Genet. 1987 Aug;41(2):119–127. [PMC free article] [PubMed] [Google Scholar]
  19. Karathanasis S. K., Yunis I., Zannis V. I. Structure, evolution, and tissue-specific synthesis of human apolipoprotein AIV. Biochemistry. 1986 Jul 1;25(13):3962–3970. doi: 10.1021/bi00361a034. [DOI] [PubMed] [Google Scholar]
  20. Kratzin H., Armstrong V. W., Niehaus M., Hilschmann N., Seidel D. Structural relationship of an apolipoprotein (a) phenotype (570 kDa) to plasminogen: homologous kringle domains are linked by carbohydrate-rich regions. Biol Chem Hoppe Seyler. 1987 Dec;368(12):1533–1544. doi: 10.1515/bchm3.1987.368.2.1533. [DOI] [PubMed] [Google Scholar]
  21. Krempler F., Kostner G. M., Bolzano K., Sandhofer F. Turnover of lipoprotein (a) in man. J Clin Invest. 1980 Jun;65(6):1483–1490. doi: 10.1172/JCI109813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lewis J. H., Bontempo F. A., Spero J. A., Ragni M. V., Starzl T. E. Liver transplantation in a hemophiliac. N Engl J Med. 1985 May 2;312(18):1189–1190. doi: 10.1056/NEJM198505023121812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lin-Lee Y. C., Kao F. T., Cheung P., Chan L. Apolipoprotein E gene mapping and expression: localization of the structural gene to human chromosome 19 and expression of ApoE mRNA in lipoprotein- and non-lipoprotein-producing tissues. Biochemistry. 1985 Jul 2;24(14):3751–3756. doi: 10.1021/bi00335a050. [DOI] [PubMed] [Google Scholar]
  24. Lin C. T., Xu Y. F., Wu J. Y., Chan L. Immunoreactive apolipoprotein E is a widely distributed cellular protein. Immunohistochemical localization of apolipoprotein E in baboon tissues. J Clin Invest. 1986 Oct;78(4):947–958. doi: 10.1172/JCI112685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lin N. S., Langenberg W. G. Immunohistochemical localization of barley stripe mosaic virions in infected wheat cells. J Ultrastruct Res. 1983 Jul;84(1):16–23. doi: 10.1016/s0022-5320(83)90082-5. [DOI] [PubMed] [Google Scholar]
  26. Menzel H. J., Boerwinkle E., Schrangl-Will S., Utermann G. Human apolipoprotein A-IV polymorphism: frequency and effect on lipid and lipoprotein levels. Hum Genet. 1988 Aug;79(4):368–372. doi: 10.1007/BF00282179. [DOI] [PubMed] [Google Scholar]
  27. Menzel H. J., Kövary P. M., Assmann G. Apolipoprotein A-IV polymorphism in man. Hum Genet. 1982;62(4):349–352. doi: 10.1007/BF00304554. [DOI] [PubMed] [Google Scholar]
  28. Newman T. C., Dawson P. A., Rudel L. L., Williams D. L. Quantitation of apolipoprotein E mRNA in the liver and peripheral tissues of nonhuman primates. J Biol Chem. 1985 Feb 25;260(4):2452–2457. [PubMed] [Google Scholar]
  29. Sing C. F., Schultz J. S., Shreffler D. C. The genetics of the Lp antigen. II. A family study and proposed models of genetic control. Ann Hum Genet. 1974 Jul;38(1):47–56. doi: 10.1111/j.1469-1809.1974.tb01992.x. [DOI] [PubMed] [Google Scholar]
  30. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Utermann G., Hees M., Steinmetz A. Polymorphism of apolipoprotein E and occurrence of dysbetalipoproteinaemia in man. Nature. 1977 Oct 13;269(5629):604–607. doi: 10.1038/269604a0. [DOI] [PubMed] [Google Scholar]
  32. Utermann G., Menzel H. J., Kraft H. G., Duba H. C., Kemmler H. G., Seitz C. Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. J Clin Invest. 1987 Aug;80(2):458–465. doi: 10.1172/JCI113093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Utermann G., Steinmetz A., Weber W. Genetic control of human apolipoprotein E polymorphism: comparison of one- and two-dimensional techniques of isoprotein analysis. Hum Genet. 1982;60(4):344–351. doi: 10.1007/BF00569216. [DOI] [PubMed] [Google Scholar]
  34. Utermann G., Weisgraber K. H., Weber W., Mahley R. W. Genetic polymorphism of apolipoprotein E: a variant form of apolipoprotein E2 distinguished by sodium dodecyl sulfate--polyacrylamide gel electrophoresis. J Lipid Res. 1984 Apr;25(4):378–382. [PubMed] [Google Scholar]
  35. Williams D. L., Dawson P. A., Newman T. C., Rudel L. L. Apolipoprotein E synthesis in peripheral tissues of nonhuman primates. J Biol Chem. 1985 Feb 25;260(4):2444–2451. [PubMed] [Google Scholar]
  36. 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