Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1987 Aug;80(2):458–465. doi: 10.1172/JCI113093

Lp(a) glycoprotein phenotypes. Inheritance and relation to Lp(a)-lipoprotein concentrations in plasma.

G Utermann, H J Menzel, H G Kraft, H C Duba, H G Kemmler, C Seitz
PMCID: PMC442258  PMID: 2956279

Abstract

The Lp(a) lipoprotein represents a quantitative genetic trait. It contains two different polypeptide chains, the Lp(a) glycoprotein and apo B-100. We have demonstrated the Lp(a) glycoprotein directly in human sera by sodium dodecyl sulfate-gel electrophoresis under reducing conditions after immunoblotting using anti-Lp(a) serum and have observed inter- and intraindividual size heterogeneity of the glycoprotein with apparent molecular weights ranging from approximately 400,000-700,000 D. According to their relative mobilities compared with apo B-100 Lp(a) patterns were categorized into phenotypes F (faster than apo B-100), B (similar to apo B-100), S1, S2, S3, and S4 (all slower than apo B-100), and into the respective double-band phenotypes. Results from neuraminidase treatment of isolated Lp(a) glycoprotein indicate that the phenotypic differences do not reside in the sialic acid moiety of the glycoprotein. Family studies are compatible with the concept that Lp(a) glycoprotein phenotypes are controlled by a series of autosomal alleles (Lp[a]F, Lp[a]B, Lp[a]S1, Lp[a]S2, Lp[a]S3, Lp[a]S4, and Lp[a]0) at a single locus. Comparison of Lp(a) plasma concentrations in different phenotypes revealed a highly significant association of phenotype with concentration. Phenotypes B, S1, and S2 are associated with high and phenotypes S3 and S4 with low Lp(a) concentrations. This suggests that the same gene locus is involved in determining Lp(a) glycoprotein phenotypes and Lp(a) lipoprotein concentrations in plasma and is the first indication for structural differences underlying the quantitative genetic Lp(a)-trait.

Full text

PDF
458

Images in this article

Selected References

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

  1. Albers J. J., Hazzard W. R. Immunochemical quantification of human plasma Lp(a) lipoprotein. Lipids. 1974 Jan;9(1):15–26. doi: 10.1007/BF02533209. [DOI] [PubMed] [Google Scholar]
  2. Armstrong V. W., Walli A. K., Seidel D. Isolation, characterization, and uptake in human fibroblasts of an apo(a)-free lipoprotein obtained on reduction of lipoprotein(a). J Lipid Res. 1985 Nov;26(11):1314–1323. [PubMed] [Google Scholar]
  3. 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]
  4. Beisiegel U., Utermann G. An apolipoprotein homolog of rat apolipoprotein A-IV in human plasma. Isolation and partial characterisation. Eur J Biochem. 1979 Feb 1;93(3):601–608. doi: 10.1111/j.1432-1033.1979.tb12860.x. [DOI] [PubMed] [Google Scholar]
  5. Berg K., Dahlén G., Frick M. H. Lp(a) lipoprotein and pre-beta1-lipoprotein in patients with coronary heart disease. Clin Genet. 1974;6(3):230–235. doi: 10.1111/j.1399-0004.1974.tb00657.x. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Ehnholm C., Garoff H., Renkonen O., Simons K. Protein and carbohydrate composition of Lp(a)lipoprotein from human plasma. Biochemistry. 1972 Aug 15;11(17):3229–3232. doi: 10.1021/bi00767a015. [DOI] [PubMed] [Google Scholar]
  8. Ehnholm C., Garoff H., Simons K., Aro H. Purification and quantitation of the human plasma lipoprotein carrying the Lp(a) antigen. Biochim Biophys Acta. 1971 May 25;236(2):431–439. doi: 10.1016/0005-2795(71)90223-6. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Fless G. M., ZumMallen M. E., Scanu A. M. Isolation of apolipoprotein(a) from lipoprotein(a). J Lipid Res. 1985 Oct;26(10):1224–1229. [PubMed] [Google Scholar]
  11. 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]
  12. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  13. Harvie N. R., Schultz J. S. Studies of Lp-lipoprotein as a quantitative genetic trait. Proc Natl Acad Sci U S A. 1970 May;66(1):99–103. doi: 10.1073/pnas.66.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Harvie N. R., Schultz J. S. Studies on the heterogeneity of human serum Lp lipoproteins and on the occurrence of double Lp lipoprotein variants. Biochem Genet. 1973 Jul;9(3):235–245. doi: 10.1007/BF00485737. [DOI] [PubMed] [Google Scholar]
  15. Hasstedt S. J., Wilson D. E., Edwards C. Q., Cannon W. N., Carmelli D., Williams R. R. The genetics of quantitative plasma Lp(a): analysis of a large pedigree. Am J Med Genet. 1983 Oct;16(2):179–188. doi: 10.1002/ajmg.1320160208. [DOI] [PubMed] [Google Scholar]
  16. Havekes L., Vermeer B. J., Brugman T., Emeis J. Binding of LP(a) to the low density lipoprotein receptor of human fibroblasts. FEBS Lett. 1981 Sep 28;132(2):169–173. doi: 10.1016/0014-5793(81)81153-2. [DOI] [PubMed] [Google Scholar]
  17. Kostner G. M., Avogaro P., Cazzolato G., Marth E., Bittolo-Bon G., Qunici G. B. Lipoprotein Lp(a) and the risk for myocardial infarction. Atherosclerosis. 1981 Jan-Feb;38(1-2):51–61. doi: 10.1016/0021-9150(81)90103-9. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Krempler F., Kostner G. M., Roscher A., Haslauer F., Bolzano K., Sandhofer F. Studies on the role of specific cell surface receptors in the removal of lipoprotein (a) in man. J Clin Invest. 1983 May;71(5):1431–1441. doi: 10.1172/JCI110896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Krempler F., Kostner G., Bolzano K., Sandhofer F. Lipoprotein (a) is not a metabolic product of other lipoproteins containing apolipoprotein B. Biochim Biophys Acta. 1979 Oct 26;575(1):63–70. doi: 10.1016/0005-2760(79)90131-0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Maartmann-Moe K., Berg K. Lp(a) lipoprotein enters cultured fibroblasts independently of the plasma membrane low density lipoprotein receptor. Clin Genet. 1981 Nov;20(5):352–362. doi: 10.1111/j.1399-0004.1981.tb01047.x. [DOI] [PubMed] [Google Scholar]
  23. Moeremans M., Daneels G., Van Dijck A., Langanger G., De Mey J. Sensitive visualization of antigen-antibody reactions in dot and blot immune overlay assays with immunogold and immunogold/silver staining. J Immunol Methods. 1984 Nov 30;74(2):353–360. doi: 10.1016/0022-1759(84)90303-x. [DOI] [PubMed] [Google Scholar]
  24. Neville D. M., Jr Molecular weight determination of protein-dodecyl sulfate complexes by gel electrophoresis in a discontinuous buffer system. J Biol Chem. 1971 Oct 25;246(20):6328–6334. [PubMed] [Google Scholar]
  25. Poduslo J. F. Glycoprotein molecular-weight estimation using sodium dodecyl sulfate-pore gradient electrophoresis: comparison of tris-glycine and tris-borate-EDTA buffer systems. Anal Biochem. 1981 Jun;114(1):131–139. doi: 10.1016/0003-2697(81)90463-2. [DOI] [PubMed] [Google Scholar]
  26. Redgrave T. G., Roberts D. C., West C. E. Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal Biochem. 1975 May 12;65(1-2):42–49. doi: 10.1016/0003-2697(75)90488-1. [DOI] [PubMed] [Google Scholar]
  27. Renninger W., Wendt G. G., Nawrocki P., Weigand H. Beitrag zur Problematik des Lp-Systems. Humangenetik. 1965;1(7):658–667. [PubMed] [Google Scholar]
  28. Rhoads G. G., Morton N. E., Gulbrandsen C. L., Kagan A. Sinking pre-beta lipoprotein and coronary heart disease in Japanese-American men in Hawaii. Am J Epidemiol. 1978 Nov;108(5):350–356. doi: 10.1093/oxfordjournals.aje.a112631. [DOI] [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., Menzel H. J., Adler G., Dieker P., Weber W. Substitution in vitro of lecithin-cholesterol acyltransferase. Analysis of changes in plasma lipoproteins. Eur J Biochem. 1980;107(1):225–241. doi: 10.1111/j.1432-1033.1980.tb04643.x. [DOI] [PubMed] [Google Scholar]
  32. Utermann G., Weber W. Protein composition of Lp(a) lipoprotein from human plasma. FEBS Lett. 1983 Apr 18;154(2):357–361. doi: 10.1016/0014-5793(83)80182-3. [DOI] [PubMed] [Google Scholar]
  33. Wiegandt H., Lipp K., Wendt G. G. Identifizierung eines Lipoproteins mit Antigenwirksamkeit im Lp-System. Hoppe Seylers Z Physiol Chem. 1968 Apr;349(4):489–494. [PubMed] [Google Scholar]

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

RESOURCES