Multi-modal expression of apolipoprotein (a) gene in vivo.

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.