The
apolipoprotein (a) [
apo(a)] gene encodes a
protein component of
lipoprotein (a) [Lp(a)] whose plasma levels vary among individuals. To study the implications of Lp(a), we examined plasma Lp(a) levels and molecular weights of
apo(a) in patients with
cerebrovascular disease (CVD) or
diabetes mellitus (DN). Mean Lp(a) concentrations were higher in the CVD cases with atherothrombotic
brain infarction than in those with
brain hemorrhage and
lacunar infarction. Lp(a) levels were lower in the DM cases on
diet therapy alone than in those treated with
insulin or oral
hypoglycemic agents. These results suggest that Lp(a) is thrombogenic and atherogenic, and that
insulin may modulate Lp(a) levels. We subclassified the
apo(a) gene into four types (A-D) by polymorphisms in the 5'-flanking region. We also measured plasma Lp(a) concentrations and examined expression of the gene by an in vitro assay. Homozygotes of type C had higher Lp(a) levels than those of type D, and the relative expression of type C was higher than that of type D in vitro. Lp(a) levels, however, varied even within the same 5'-allele having similar
apo(a)
isoforms. Thus, Lp(a) concentrations are genetically determined and may be modified by some
hormones and
cytokines. When we examined transcript levels for
apo(a) by RT-PCR in various normal tissues,
apo(a) was strongly expressed in liver while not in thyroid or leukocytes. Small amounts of
apo(a) transcript were observed in all other organs and tissues.
Apo(a) in these tissues may also play a role in inframmation, tissue remodeling, cell migration, and other physiological functions.