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. 2000 Feb 22;14(2):53–58. doi: 10.1002/(SICI)1098-2825(2000)14:2<53::AID-JCLA3>3.0.CO;2-Y

An application of apo(a) isoforms for the clinical assessment of Lp(a)

Shigenobu Takayama 1,4,✉, Yoko Yasumuro 2, Jae‐hyuk Kim 3, Masashi Ishikawa 3, Daijirou Tsujino 3, Sumitaka Matsuo 4, Yoshiteru Harada 4, Shunji Sugii 5
PMCID: PMC6807969  PMID: 10683614

Abstract

To examine whether or not Lp(a) is applicable as a diagnostic marker for atherosclerosis, we studied the correlation between Lp(a) levels and molecular weights of apo(a) isoforms in sera from both normal healthy adults and diabetic patients. Serum Lp(a) level was measured by turbidimetric immunoassay (TIA) and the molecular weight of apo(a) isoform was determined by Western blotting analysis. The serum Lp(a) levels of the diabetic patients (25.0 mg/dl ± 2.2 [mean ± SE], n = 54) were significantly higher than those of the normal subjects (14.4 mg/dl ± 0.57, n = 500). With respect to the correlation between serum Lp(a) levels and the molecular weights of apo(a) isoforms, there was an inverse correlation in sera from normal subjects (n = 298), whereas there was no correlation in sera from the diabetic patients. Statistical significant inverse correlation (r = –0.91, y = 224.25 – 3.07×) was especially observed in 50 representative apo(a) isotypes from the normal subjects. By applying a standardized curve based on the significant inverse correlation to serum Lp(a) levels, 40.7% (22/54) of the diabetic patients were revealed to have an abnormally high value of serum Lp(a). Moreover, it was found that the significantly higher mean value of serum Lp(a) in the diabetic group was caused by the 22 patients with higher value of Lp(a). The present findings suggest that determination of apo(a) isoform size provides estimation of the serum Lp(a) value and that the inverse correlation curve between serum Lp(a) level and the molecular weight of apo(a) isoform may be applicable to the clinical use of Lp(a). J. Clin. Lab. Anal. 14:53–58, 2000. © 2000 Wiley‐Liss, Inc.

Keywords: Lp(a) level, apo(a) isoform, inheriting plasma protein, inverse correlation

REFERENCES

  • 1. Berg K. A new serum type system in man‐the Lp‐system. Acta. Pathol. Microbiol. Scand 1963;59:369–382. [DOI] [PubMed] [Google Scholar]
  • 2. Fless GM, Rolih CA, Scanu AM. Heterogeneity of human plasma lipoprotein(a). Isolation and characterization of the lipoprotein subspecies and their apoproteins. J Biol Chem 1984;259:1470–1478. [PubMed] [Google Scholar]
  • 3. Fless GM, ZumMallen ME, Scanu AM. Isolation of apolipoprotein(a) from lipoprotein(a). J Lipid Res 1985;26:1224–1229. [PubMed] [Google Scholar]
  • 4. Gaubatz JW, Heideman C, Gotto AM Jr, Morrisett JD, Dahlen GH. Human plasma lipoprotein[a]. Structural properties. J Biol Chem 1983;258:4582–4589. [PubMed] [Google Scholar]
  • 5. Gaw A, Boerwinkle E, Cohen LC, Hobbs HH. Comparative analysis of the apo(a) gene, apo(a) glycoprotein, and plasma concentrations of Lp(a) in three ethnic groups. J Clin Invest 1994;93:2526–2534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Scanu AM. Stractural and functional polymorphism of lipoprotein (a): biological and clinical implications. Clin Chem 1995;41:170–172. [PubMed] [Google Scholar]
  • 7. Trieu VN, Zioncheck TF, Lawn RM, McConathy WJ. Interaction of apolipoprotein(a) with apolipoprotein B‐containing lipoproteins. J Biol Chem 1991;266:5480–5485. [PubMed] [Google Scholar]
  • 8. Utermann G, Menzel HJ, Kraft HG, Duba CH, Kemmler HG, Seitz C. Lp(a) glycoprotein phenotype. Inheritance and relation to Lp(a)‐lipoprotein concentration in plasma. J Clin Invest 1987;80:458–465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Loscalzo J. Lipoprotein (a). A unique risk factor for atherothrombotic disease. Atherosclerosis 1990;10:672–679. [DOI] [PubMed] [Google Scholar]
  • 10. Sandkamp M, Funke H, Schulte H, Kohler E, Assmann G. Lipoprotein (a) is an independent risk factor for myocardial infarction at a young age. Clin Chem 1990;36:20–23. [PubMed] [Google Scholar]
  • 11. Armstrong VW, Cremer P, Eberle E, et al. The association between serum Lp(a) concentration and angiopathically assessed coronary atherosclerosis. Dependence on serum LDL level. Atherosclerosis 1986; 62:249–257. [DOI] [PubMed] [Google Scholar]
  • 12. Dahlen GH, Guyton JR, Attar M, Farmer JA, Kautz JA, Gotto AM Jr. Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiopathy. Circulation 1986;74:758–765. [DOI] [PubMed] [Google Scholar]
  • 13. Koltringer P, Jurgens G. A dominant role of lipoprotein(a) in the development of cervical atherosclerosis. Atherosclerosis 1985;58:187–198. [DOI] [PubMed] [Google Scholar]
  • 14. Renninger W, Wendt GG, Nawrocki P, Weigand H. Contribution to problems of the Lp‐systems. Humangenetik 1965;1:658–667. [PubMed] [Google Scholar]
  • 15. Zenker G, Koltringer P, Bone G, Niederkom K, Pfeiffer KP, Jurgens G. Lipoprotein (a) as a strong indicator for cerebrovascular disease. Stroke 1986;17:942–945. [DOI] [PubMed] [Google Scholar]
  • 16. Bruckert E, Davidoff P, Grimaldi A, et al. Increased serum levels of lipoprotein(a) in diabetes mellitus and their reduction with glycemic control. JAMA 1990;263:35–36. [PubMed] [Google Scholar]
  • 17. Heller FR, Jamart J, Honore P, et al. Serum lipoprotein(a) in patient with diabetes mellitus. Diabetes Care 1993;16:819–823. [DOI] [PubMed] [Google Scholar]
  • 18. Megoro T, Ohbayashi S, Sudou T, Takayama S, Shiga K, Tateshita T. Fundamental and clinical study of TIA method for the quantification of serum Lp(a). Igaku to Yakugaku 1994;31:989–993. [Google Scholar]
  • 19. Sandholzer C, Hallmann DM, Sala N. Effects of apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups. Human Genet 1991;86:607–614. [DOI] [PubMed] [Google Scholar]
  • 20. Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest 1992;90:52–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Gaubatz JW, Ghanem KI, Guevara Jr. Nava ML, Patsch W, Morriset JD. Polymorphic forms of human apolipoprotein(a): inheritance and relationship of their molecular weights to plasma levels of lipoprotein(a). J Lipid Res 1990;31:603–613. [PubMed] [Google Scholar]
  • 22. Hsu SM, Raine L. Protein A, avidin, and biotin in immunohistochemistry. J Histochem Cytochem 1981;29:1349–1359. [DOI] [PubMed] [Google Scholar]
  • 23. Assmann G, Schutle H. The prospective cardiovascular munster (PROCAM) study: prevalence of hyperlipidemia in persons with hypertension and/or diabetes mellitus and the relationship to coronary heart disease. Am Heart J 1988;116:1713–1724. [DOI] [PubMed] [Google Scholar]
  • 24. Kannel WB, MoGee DL. Diabetes and cardiovascular risk factors. The Framingham study.Circulation 1979;59:8–13. [DOI] [PubMed] [Google Scholar]
  • 25. Stamler J, Vaccaro O, Neaton JD, Wentworth D, Group MR. Diabetes, other risk factors, and 12‐yr. cardiovascular mortality for men screened in the Multiple Risk Factor Investigation Trial. Diabetes Care 1993;16:434–444. [DOI] [PubMed] [Google Scholar]
  • 26. Wood WG, Schumacher M, Weigert S. (Apo)lipoprotein(a) concentrations at birth and in the first days and months of life—studies on the distribution of serum levels and the predictive value of measurements made at this time. Eur J Clin Chem Clin Biochem 1995;33:139–145. [DOI] [PubMed] [Google Scholar]
  • 27. Rifai N, Heiss G, Doetsch K. Lipoprotein(a) at birth, in blacks and whites. Atherosclerosis 1992;92:123–129. [DOI] [PubMed] [Google Scholar]
  • 28. Knapp RG, Schreiner PJ, Sutherland SE, et al. Serum lipoprotein(a) levels in elderly black and white men in the Charleston Heart Study. Clin Genet 1993;44:225–231. [DOI] [PubMed] [Google Scholar]
  • 29. Kario K, Matsuo T, Imiya M, et al. Close relation between lipoprotein (a) levels and atherothrombotic disease in Japanese subjects > 75 years of age. Am J Cardiol 1994;15:1187–1190. [DOI] [PubMed] [Google Scholar]
  • 30. Jenner JL, Ordovas JM, Lamon‐Fava S, Schaefer MM, Wilson PW, Castelli WP, Schaefer EJ. Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels. The Framingham Offspring Study. Circulation 1993;87:1135–1141. [DOI] [PubMed] [Google Scholar]
  • 31. Slunga L, Asplund K, Johnson O, Dahlen GH. Lipoprotein (a) in a randomly selected 25–64 year old population: the Northern Sweden Monica Study. J Clin Epidemiol 1993;46:617–624. [DOI] [PubMed] [Google Scholar]
  • 32. Brown SA, Hutchinson R, Morrisett J, Boerwinkle E, Davis CE, Gotto AM Jr, Patsch W. Plasma lipid, lipoprotein cholesterol, and apoprotein distributions in selected US communities. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb 1993;13:1139–1158. [DOI] [PubMed] [Google Scholar]
  • 33. Bovet P, Rickenbach M, Wietlisbach V, Riesen W, Shamlaye C, Darioli R, Burnand B. Comparison of serum lipoprotein(a) distribution and its correlates among black and white populations. Int J Epidemiol 1994;23:20–27. [DOI] [PubMed] [Google Scholar]
  • 34. Nago N, Kayaba K, Hiraoka J, et al. Lipoprotein(a) levels in the Japanese population: influence of age and sex, and relation to atherosclerotic risk factors. The Jichi Medical School Cohort Study. Am J Epidemiol 1995;141:815–821. [DOI] [PubMed] [Google Scholar]
  • 35. Hata Y, editor. Lipoprotein(a)—Kiso to Rinshou. Tokyo: Kyouwa Kikaku, Inc.; 1998. 267 p. [Google Scholar]

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