GeneticsLandmark
The mysteries of lipoprotein(a) (Utermann, Science 1989)
Original title: The mysteries of lipoprotein(a)
Gerd Utermann's Science review framed the questions the field spent the next three decades answering: Lp(a) is assembled from LDL and apo(a), a plasminogen-like glycoprotein; plasma concentrations vary a thousandfold between people and are a continuous, skewed, quantitative genetic trait; variation at the hypervariable apo(a) gene on 6q26-27, interacting with defective LDL-receptor alleles, explains most of that variability; and the metabolism, function and regulation of the particle were largely unknown. The genetics were already clear in 1989; the causality and the therapy took until the 2010s and 2020s.
Original abstract
Lipoprotein(a) [Lp(a)] is a macromolecular complex found in human plasma that combines structural elements from the lipoprotein and blood clotting systems and that is associated with premature coronary heart disease and stroke. It is assembled from low-density lipoprotein (LDL) and a large hydrophilic glycoprotein called apolipoprotein(a) [apo(a)], which is homologous to the protease zymogen plasminogen. Plasma Lp(a) concentrations vary 1000-fold between individuals and represent a continuous quantitative genetic trait with a skewed distribution in Caucasian populations. Variation in the hypervariable apo(a) gene on chromosome 6q2.6-q2.7 and interaction of apo(a) alleles with defective LDL-receptor genes explain a large fraction of the variability of plasma Lp(a) concentrations. Though of high theoretical and practical interest, many aspects of the metabolism, function, evolution, and regulation of plasma concentrations of Lp(a) are presently unknown, controversial, or mysterious.
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Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.