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. 1989 Dec;84(6):2021–2027. doi: 10.1172/JCI114395

Plasma Ip(a) concentration is inversely correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene.

D Gavish 1, N Azrolan 1, J L Breslow 1
PMCID: PMC304088  PMID: 2556454

Abstract

Plasma Lp(a) levels correlate with atherosclerosis susceptibility. This lipoprotein consists of an LDL-like particle attached to a large glycoprotein called apo(a). Apo(a) is a complex glycoprotein containing multiple Kringle domains, found to be highly homologous to plasminogen Kringle IV, and a single Kringle domain homologous to plasminogen Kringle V. Lp(a) levels appear to be inversely correlated with apo(a) size in a given individual. In this study, we have used probes specific to the Kringles IV and V domains of apo(a) cDNA in quantitative Southern blotting analysis. By this method, we have determined the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene of 53 unrelated individuals with different plasma concentrations of Lp(a). This ratio was found to be inversely correlated with log Lp(a) levels (r = -0.90, P less than 0.0001) and directly correlated with apo(a) apparent molecular weight (Mr) (r = 0.79, P less than 0.0001). In summary, by showing that Lp(a) concentrations and apo(a) apparent size are highly correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene, we provide a DNA marker for this atherosclerosis risk factor as well as an important insight into the genetic mechanism regulating Lp(a) levels.

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Selected References

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

  1. 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]
  2. Berg K. Twin studies of coronary heart disease and its risk factors. Acta Genet Med Gemellol (Roma) 1987;36(4):439–453. doi: 10.1017/s0001566000006814. [DOI] [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. Dahl H. H., Choo K. H., Danks D. M. Application of DNA-DNA hybridization of dual labeled probes to the detection of trisomy 21, monosomy 21, and sex determination. Am J Hum Genet. 1988 Oct;43(4):502–510. [PMC free article] [PubMed] [Google Scholar]
  5. Drayna D. T., Hegele R. A., Hass P. E., Emi M., Wu L. L., Eaton D. L., Lawn R. M., Williams R. R., White R. L., Lalouel J. M. Genetic linkage between lipoprotein(a) phenotype and a DNA polymorphism in the plasminogen gene. Genomics. 1988 Oct;3(3):230–236. doi: 10.1016/0888-7543(88)90084-5. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Forsgren M., Råden B., Israelsson M., Larsson K., Hedén L. O. Molecular cloning and characterization of a full-length cDNA clone for human plasminogen. FEBS Lett. 1987 Mar 23;213(2):254–260. doi: 10.1016/0014-5793(87)81501-6. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Gunning P., Ponte P., Okayama H., Engel J., Blau H., Kedes L. Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed. Mol Cell Biol. 1983 May;3(5):787–795. doi: 10.1128/mcb.3.5.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gurakar A., Hoeg J. M., Kostner G., Papadopoulos N. M., Brewer H. B., Jr Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment. Atherosclerosis. 1985 Nov;57(2-3):293–301. doi: 10.1016/0021-9150(85)90041-3. [DOI] [PubMed] [Google Scholar]
  12. Hoefler G., Harnoncourt F., Paschke E., Mirtl W., Pfeiffer K. H., Kostner G. M. Lipoprotein Lp(a). A risk factor for myocardial infarction. Arteriosclerosis. 1988 Jul-Aug;8(4):398–401. doi: 10.1161/01.atv.8.4.398. [DOI] [PubMed] [Google Scholar]
  13. Kostner G. M. The affection of lipoprotein-a by lipid lowering drugs. Prog Clin Biol Res. 1988;255:255–263. [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Laurell C. B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem. 1966 Apr;15(1):45–52. doi: 10.1016/0003-2697(66)90246-6. [DOI] [PubMed] [Google Scholar]
  16. McLean J. W., Tomlinson J. E., Kuang W. J., Eaton D. L., Chen E. Y., Fless G. M., Scanu A. M., Lawn R. M. cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature. 1987 Nov 12;330(6144):132–137. doi: 10.1038/330132a0. [DOI] [PubMed] [Google Scholar]
  17. Murray J. C., Buetow K. H., Donovan M., Hornung S., Motulsky A. G., Disteche C., Dyer K., Swisshelm K., Anderson J., Giblett E. Linkage disequilibrium of plasminogen polymorphisms and assignment of the gene to human chromosome 6q26-6q27. Am J Hum Genet. 1987 Apr;40(4):338–350. [PMC free article] [PubMed] [Google Scholar]
  18. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Utermann G., Kraft H. G., Menzel H. J., Hopferwieser T., Seitz C. Genetics of the quantitative Lp(a) lipoprotein trait. I. Relation of LP(a) glycoprotein phenotypes to Lp(a) lipoprotein concentrations in plasma. Hum Genet. 1988 Jan;78(1):41–46. doi: 10.1007/BF00291232. [DOI] [PubMed] [Google Scholar]
  21. 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]

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