Summary
Apolipoprotein(a) [apo(a)] is a large serum glycoprotein with several genetically determined isoforms differing in their apparent molecular weight. We determined the effects of the apo(a) isoforms on total cholesterol, high-density lipo-protein (HDL)-cholesterol, lipoprotein(a), and triglyceride levels in a sample of 473 unrelated Tyrolean adults. Average lipoprotein(a) and total cholesterol levels were significantly different among apo(a) types. These significant differences were found among the 13 apo(a) isoform patterns observed in this sample and among several logical subsets of the isoform patterns (e.g. considering only the single band types). The data suggest that the effects of apo(a) alleles on Lp(a) levels are additive. The effects of apo(a) on total cholesterol levels cannot be entirely explained by the cholesterol fraction estimated to be contained in the lipoprotein(a) particle. We estimate that the apo(a) glycoprotein polymorphism accounts for 41.9% and 9.6% of the variability in lipoprotein(a) and total cholesterol levels, respectively. This is the strongest effect of a single polymorphic gene on plasma lipid and lipoprotein levels reported so far.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Albers JJ, Cabana VG, Warnick GR, Hazzard WR (1975) Relationship to sinking pre-beta lipoprotein, hyperlipoproteinemia, and apolipoprotein B. Metabolism 24:1047–1054
Armstrong VW, Walli AK, Seidel D (1985) Isolation, characterization and uptake in human fibroblasts of an apo (a)-free lipoprotein obtained on reduction of lipoprotein (a). J Lipid Res 26:1314–1323
Berg K (1963) A new serum type system in man—the 1p system. Acta Pathol Microbiol Scand 59:369–382
Berg K (1983) Genetics of coronary heart disease. Prog Med Genet 5:35–90
Boerwinkle E, Sing CF (1986) Bias of the contribution of single locus effects to the variance of a quantitative trait. Am J Hum Genet 39:137–144
Boerwinkle E, Utermann G (1988) Simultaneous effects of the apolipoprotein E polymorphism on apolipoprotein E, apolipoprotein B and cholesterol metabolism. Am J Hum Genet 42:104–112
Boerwinkle E, Chakraborty R, Sing CF (1986) The use of measured genotype information in the analysis of quantitative phenotypes in man. I. Models and analytical methods. Ann Hum Genet 50:181–194
Brown MS, Goldstein JL (1987) Plasma lipoproteins: teaching old dogmas new tricks. Nature 330:113–114
Conover WJ (1980) Practical nonparametric statistics. Wiley, New York
Dahlen GH, Guyton JR, Mohammad A, Farmer JA, Kautz JA, Gotto AM (1986) Association of levels of lipoprotein Lp(a), plasma lipids and other lipoproteins with coronary artery disease documented by angiography. Circulation 74:758–765
Day NE (1969) Estimating the components of a mixture of normal distributions. Biometrika 56:463–474
Ehnholm C, Garoff H, Renkonen O, Simons K (1972) Protein and carbohydrate composition of Lp(a) lipoprotein from human plasma. Biochemistry 11:3229–3232
Fleiss JL (1981) Statistical methods for rates and proportions. Wiley, New York
Fless GM, Rolik CA, Scanu AM (1984) Heterogeneity of human plasma lipoprotein(a). Isolation and characterization of the lipoprotein subspecies and their apoproteins. J Biol Chem 259: 11470–11478
Fless GM, Zum Mallen ME, Scanu AM (1986) Physiological properties of apolippprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein(a). J Biol Chem 261: 8712–8718
Gaubatz JW, Heideman C, Gotto AM, Morrisett JD, Dahlen GH (1983) Human plasma lipoprotein(a): structural properties. J Biol Chem 258:4582–4589
Hasselblad V (1966) Estimation of parameters for a mixture of normal distributions. Technometrics 8:431–444
Hassted SJ, Williams RR (1986) Three alleles for quantitative Lp(a). Genet Epidemiol 3:53–55
Havekes L, Vermeer T, Brugman T, Emeis J (1981) Binding of Lp(a) to the low density lipoprotein receptor of human fibroblasts. FEBS Lett 132:169–173
Kratzin H, Armstrong VW, Niehaus M, Hilschmann N, Seidel D (1987) Structural relationship of an apolipoprotein(a) phenotype (570 K Da) to plasminogen: homologous kringle domains are linked by carbohydrate-rich regions. Hoppe-Seylers Z Biol Chem 368:1533–1544
Krempler F, Kostner GM, Bolzano K, Sandhofer F (1980) Turnover of lipoprotein(a) in man. J Clin Invest 65:1483–1490
Maartman-Moe K, Berg K (1981) Lp(a) enters cultured fibroblasts independently of the plasma membrane low density lipoprotein receptor. Clin Genet 20:352–362
McLean JW, Tomlinson JE, Kuang W, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM (1987) cDNA Sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 330: 132–137
Morrisett JD, Guyton JR, Gaubatz JW, Gotto AM Jr (1987) Lipoprotein (a): structure, metabolism and epidemiology. In: Goto AM Jr (ed) Plasma lipoproteins. (New comprehensive biochemistry, vol 14) Elsevier, Amsterdam, pp 129–152
Morton NE, Berg K, Dahlen G, Ferrel RE, Rhoads GG (1985) Genetics of Lp lipoprotein in Japanese-Americans. Genet Epidemiol 2:113–121
Neter JW, Wasserman W, Kutner MH (1985) Applied linear statistical models. Irwin, Homewood, Ill
Rhoads GG, Dahlen G, Berg K, Morton NE, Dannenberg AL (1986) Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA 256:2540–2544
Scheffe H (1959) The analysis of variance. Wiley, New York
Sing CF, Schultz JS, Schreffler DG (1974) The genetics of the 1p antigen. II. A family study and proposed models of genetic control. Ann Hum Genet 38:47–56b
Utermann G, Weber W (1983) Protein composition of Lp(a) lipoprotein from human plasma. FEBS Lett 154:357–361
Utermann G, Menzel HJ, Kraft HG, Duba C, Kemmler HG, Seitz C (1987) Lp(a) glycoprotein phenotypes: inheritance and relation to Lp(a) lipoprotein concentrations in plasma. J Clin Invest 80:458–465
Utermann G, Duba C, Menzel HJ (1988a) Genetics of the quantitative Lp(a) lipoprotein trait. II. Inheritance of Lp(a) glycoprotein phenotypes. Hum Genet 78:47–50
Utermann G, Kraft HG, Menzel HJ, Hopferwieser T, Seitz C (1988b) Genetics of the quantitative Lp(a) lipoprotein trait. I. Relation of Lp(a) glycoprotein phenotypes to Lp(a) concentrations in plasma. Hum Genet 78:41–46
Vessby B, Kostner G, Lithell H, Thomis J (1982) Diverging effects of cholestyramine on apolipoprotein B and lipoprotein (a). Atherosclerosis 44:61–71
Vogel F, Motulsky AG (1986) Human genetics—problems and approaches, 2nd edn. Springer, Berlin Heidelberg New York
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Boerwinkle, E., Menzel, H.J., Kraft, H.G. et al. Genetics of the quantitative Lp(a) lipoprotein trait. Hum Genet 82, 73–78 (1989). https://doi.org/10.1007/BF00288277
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00288277