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Genetics of the quantitative Lp(a) lipoprotein trait

I. Relation of Lp(a) glycoprotein phenotypes to Lp(a) lipoprotein concentrations in plasma

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Summary

The Lp(a) lipoprotein is a complex particle composed of a low density lipoprotein (LDL)-like lipoprotein and the disulfide bonded Lp(a) glycoprotein. The complex represents a quantitative genetic trait. SDS gel electrophoresis under reducing conditions of sera followed by immunoblotting with affinity-purified polyclonal anti-Lp(a) demonstrated inter-and intra-individual size heterogeneity of the glycoprotein with apparent Mr in the range 400–700 kDa. According to their relative mobilities compared to apo B-100 the Lp(a) patterns were categorized into phenotypes F, B, S1, S2, S3 und S4 and into the respective double-band phenotypes. This size heterogeneity seems to be controlled by multiple alleles designated LpF, LpB, LpS1, LpS2, LpS3, LpS4 and a null allele (Lpo) at a single locus. Phenotype frequencies observed in 441 unrelated subjects were in good agreement with those expected from the genetic hypothesis. Comparison of Lp(a) lipoprotein concentrations in the different phenotypes revealed a highly significant association of phenotypes B, S1 and S2 with high, and phenotypes S3 und S4 with intermediate Lp(a) concentrations. A third mode is represented by the null phenotype were no Lp(a) band is detected upon immunoblotting and Lp(a) lipoprotein is low or absent. We conclude that the same gene locus is involved in determining Lp(a) glycoprotein phenotype and Lp(a) lipoprotein concentrations in plasma. This major gene seems to be the Lp(a) glycoprotein structural gene locus.

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Authors and Affiliations

  1. Institut für Medizinische Biologie und Genetik der Universität, Schöpfstrasse 41, A-6020, Innsbruck, Austria

    Gerd Utermann, Hans Georg Kraft & Hans Jürgen Menzel

  2. Landeskrankenhaus, Universitäts-Klinik für Innere Medizin, Anichstrasse 35, A-6010, Innsbruck, Austria

    Thomas Hopferwieser

  3. Institut für Humangenetik der Universität, Bahnhofstrasse 7a, D-3550, Marburg/Lahn, Germany

    Christoph Seitz

Authors
  1. Gerd Utermann
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  2. Hans Georg Kraft
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  3. Hans Jürgen Menzel
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  4. Thomas Hopferwieser
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  5. Christoph Seitz
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Utermann, G., Kraft, H.G., Menzel, H.J. et al. Genetics of the quantitative Lp(a) lipoprotein trait. Hum Genet 78, 41–46 (1988). https://doi.org/10.1007/BF00291232

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  • DOI: https://doi.org/10.1007/BF00291232

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