€750

Lipid Metabolism & Cardiovascular Disease Genes

APOB (Apolipoprotein B)
- Function: Encodes apolipoprotein B, a major component of low-density lipoprotein (LDL), which carries cholesterol in the blood.
- Mutations cause:
  - Familial hypercholesterolaemia (FH) (when defective, LDL is not properly cleared, leading to high cholesterol and heart disease).
  - Hypobetalipoproteinaemia (when truncated, it leads to abnormally low cholesterol levels).
APOE (Apolipoprotein E)
- Function: Regulates cholesterol transport and metabolism.
- Three common variants (E2, E3, E4):
  - E2 variant – Associated with lower LDL levels but increased risk of Type III hyperlipoproteinaemia.
  - E3 variant – Most common, neutral effect.
  - E4 variant – Associated with higher cholesterol, increased cardiovascular risk, and Alzheimer’s disease.

LDL Receptor & Cholesterol Regulation

LDLR (Low-Density Lipoprotein Receptor)
- Function: Removes LDL (bad cholesterol) from the bloodstream by binding and internalising it in the liver.
- Mutations cause:
  - Familial hypercholesterolaemia (FH) – A genetic disorder that leads to severely high LDL levels and early-onset heart disease.
LDLRAP1 (Low-Density Lipoprotein Receptor Adaptor Protein 1)
- Function: Helps LDL receptors remove LDL cholesterol efficiently.
- Mutations cause:
  - Autosomal recessive hypercholesterolaemia (ARH) – A rare, inherited disorder leading to severe high cholesterol and premature cardiovascular disease.

Cholesterol Regulation & Enzyme Activity

PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9)
- Function: Controls LDL receptor degradation. Higher PCSK9 activity reduces the number of LDL receptors, leading to higher LDL cholesterol levels.
- Mutations cause:
  - Gain-of-function mutations: Increase PCSK9 activity → High cholesterol & cardiovascular disease risk.
  - Loss-of-function mutations: Reduce PCSK9 activity → Low cholesterol & reduced heart disease risk (basis for PCSK9 inhibitor drugs).