Apolipoprotein(a) gene (LPA) (LPA)

The Apolipoprotein(a) gene (LPA) encodes the apolipoprotein(a) protein, which is the defining component of the lipoprotein(a) [Lp(a)] particle (NCBI Gene ID: 4018). Lp(a) is structurally similar to low-density lipoprotein (LDL) but contains the unique apolipoprotein(a) moiety, which confers additional pro-thrombotic and pro-inflammatory properties (UniProt P08519). Elevated levels of Lp(a) are a potent, genetically determined risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis, as they are largely unaffected by lifestyle changes or statin therapy (Tsimikas, J Am Coll Cardiol, 2017). Modern therapeutic approaches target the LPA genomic locus or its mRNA transcript to lower Lp(a) production. These include antisense oligonucleotides like Pelacarsen and small interfering RNAs like Olpasiran that trigger mRNA degradation, as well as CRISPR-based base editing (e.g., VERVE-201) designed to permanently disrupt the gene's expression in the liver (Verve Therapeutics, 2024). By targeting the LPA gene directly, these therapies aim to provide a durable reduction in Lp(a) levels and decrease the incidence of cardiovascular events in high-risk populations.

Other names

LPALipoprotein(a) geneApo(a) geneLPGenomic DNA locus within LPA gene

Inhibition of gene expression via antisense oligonucleotides, RNA interference, or permanent genomic disruption through base editing to reduce circulating Lipoprotein(a) levels.