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Lipoprotein(a) gene (LPA)

Target: LPA
Molecular classification: Plasma glycoprotein (structural gene product)

Overview

The Lipoprotein(a) gene (LPA) encodes apolipoprotein(a), a glycoprotein found in plasma as part of the lipoprotein(a) [Lp(a)] particle. Lp(a) is an LDL-like particle containing apoB-100 and apo(a), linked by a disulfide bond. Plasma concentrations of Lp(a) are primarily determined by genetic variants in the LPA gene, notably the kringle IV repeat number polymorphism. Elevated Lp(a) is a significant and independent genetic risk factor for atherosclerosis, coronary artery disease, stroke, and aortic stenosis. Novel therapeutics, including antisense oligonucleotides and siRNAs, are in development to lower Lp(a) by targeting LPA gene expression.

Other names: Apolipoprotein(a) geneApo(a) geneLp(a) geneENSG00000198670MIM 152200

Mechanism of action

Inhibition of LPA gene transcription (siRNA) or translation (ASO) leading to reduced apolipoprotein(a), lowering Lp(a) particles

Biological functions

Carrier protein for lipoprotein(a)Determinant of plasma Lp(a) concentrationModulator of lipid metabolismMediator of cardiovascular risk

Disease associations

Cardiovascular disease (major independent risk factor for atherosclerosis, coronary heart disease, stroke, calcific aortic stenosis)Potentially involved in thrombosis and inflammatory processes

Safety considerations

Potential bleeding risk if Lp(a) is excessively lowered (given structural homology to plasminogen); not fully establishedOff-target effects of gene silencing drugs (siRNA, ASO)

Interacting drugs

Pelacarsen (TQJ230; antisense oligonucleotide targeting apo[a] mRNA)

2 more in the full profile.

Biomarkers

Plasma lipoprotein(a) concentration (measured in mg/dL or nmol/L; used as a biomarker of cardiovascular risk)

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