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Apolipoprotein(a) gene locus (LPA)
- Target
- LPA
- Molecular classification
- Protein-coding gene, Plasma lipoprotein gene, Other (specific: member of the apolipoprotein family)
01
Overview
The "LPA gene locus" is located on chromosome 6q25.3–q26 and encodes "apolipoprotein(a)", which covalently attaches to an LDL-like particle to form "lipoprotein(a)" (Lp(a)). Lp(a) is highly heritable, with plasma levels dictated by size polymorphisms in kringle IV repeats, and is an independent, causal factor for cardiovascular disease—most notably atherosclerosis and related endpoints like coronary heart disease and stroke. Lp(a) has a multifaceted pathogenic role, both in lipid transport and modulating blood clotting. The LPA locus is a major focus for drug development, especially gene-targeted and RNA-targeted therapies to lower Lp(a) and reduce residual cardiovascular risk. Elevated Lp(a) is also a biomarker for patient stratification and risk assessment.
- Other names
- Apolipoprotein(a) geneLp(a) gene locusLPA geneLipoprotein(a) gene
02
Mechanism of action
Lowering apolipoprotein(a) or Lp(a) synthesis (antisense therapy); Modulating lipid metabolism (PCSK9 inhibitors); Blocking IL-6 or inflammatory signaling to reduce expression
03
Biological functions
Lipid transportCarrier of oxidized phospholipidsModulation of fibrinolysis (influences blood clotting)Regulation of wound healing (suggested)Carrier protein for lipids and cholesterolOther (role in inflammation via interaction with cytokines like IL-6)
04
Disease associations
Cardiovascular disease (CHD, atherosclerosis, myocardial infarction, stroke)Aortic-valve calcificationPeripheral arterial diseaseOther (possible links to inflammation)
05
Safety considerations
Residual risk in treated individuals—high Lp(a) may persist despite statin therapyProthrombotic risk (promotes clot formation, impairs fibrinolysis)Genetic variability and population differences in Lp(a) levels
06
Interacting drugs
PCSK9 inhibitors (lower Lp(a))
3 more in the full profile.
07
Biomarkers
Serum Lp(a) concentration (primary biomarker)Allelic variants or copy number variation of LPA (kringle IV repeats, e.g., KIV-2 VNTR)Specific SNPs (e.g., rs10455872)
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