Genetic basis and pathophysiological implications of high plasma Lp(a) levels

Abstract

Lipoprotein(a) or Lp(a) is a genetic variant of plasma low density lipoproteins (LDL) containing apoB100 covalently linked to apolipoprotein(a) or apo(a), the specific marker of Lp(a). Lp(a) is heterogeneous in size and density, accounting in part for the marked size polymorphism of apo(a), 300 to 800 kDa. The apo(a) size polymorphism is related to the different number of kringle repeats which are structurally similar although not identical to the kringle 4 of plasminogen. Recent studies on a genomic level have indicated that the apo(a) gene contains at least 19 different alleles varying in length between 48 and 190 kb, partially impacting on the plasma levels of Lp(a). High plasma levels of Lp(a) have been found to be associated with an increased prevalence of premature atherosclerotic cardiovascular disease by mechanism(s) yet to be established. Both atherogenic and thrombogenic potentials have been postulated and have been related to the LDL-like and plasminogen-like properties of Lp(a), respectively.