Apo(a) is a protein found covalently linked to apo-B100 in
some LDL particles. Those LDL particles to which apo(a)
is attached are called lipoprotein(a) or Lp(a). Plasma levels
of Lp(a) correlate with increased cardiovascular disease
risk in most populations, but not in African-Americans. The level of Lp(a) appears to be entirely genetically determined.
The Lp(a) concentration is almost entirely related
to the particular alleles of the Lp(a) gene expressed by an
The Lp(a) gene is highly polymorphic (variable in structure).
Thus, it appears that most individuals have different
forms of the gene. The reason for this unusually high degree
of genetic variability is that the gene comprises multiple
repeat structures. Repeat structures lead to unequal
crossing over during meiosis, causing the production of
new variants of the gene in the offspring. The repeat structures
are domains termed “kringle domains.” The kringle
domain that is repeated in the apo(a) gene is homologous
to a kringle domain of plasminogen, an enzyme involved
in the dissolution of fibrin clots.
Why is Lp(a) so strongly correlated with risk of CHD?
Because of its homology with plasminogen, it has been
suggested that Lp(a) competes with plasmin for binding
to fibrin clots and therefore would tend to be antithrombolytic.
Another hypothesis is that Lp(a) might be
atherogenic because it has been shown in vitro to stimulate
smooth muscle cell proliferation, a hallmark of the