Apolipoproteins

Synonym: apoprotein

Lipoproteins are complexes of lipid and protein, whose main function is to transport lipids. Apolipoproteins are proteins found in the external phospholipid layer of the lipoproteins. They are important in maintaining the structural integrity and solubility of lipoproteins, play an important role in lipoprotein receptor recognition and also the regulation of certain enzymes in lipoprotein metabolism. There are many different apolipoproteins, including:

• Apo A1: the major apoprotein of HDL and is a relatively abundant plasma protein.¹
• Apo A5: influences on triglycerides through an unknown mechanism; the ApoA5 gene is considered as a probable biochemical and genetic marker of increased triglyceride concentrations and also a risk factor of coronary disease in some populations.²
• Apo B: the main apolipoprotein of chylomicrons and low density lipoproteins.³
  • Apolipoprotein B is a measurement of the total number of atherogenic particles and is therefore thought to be a better marker of risk of vascular disease and a better guide to the adequacy of statin treatment than any cholesterol index.⁴
  • The ratio of apolipoprotein B/apolipoprotein A-1 seems superior to the ratio of total cholesterol/HDL cholesterol as an overall index of the risk of vascular disease.⁴
  • Apo B and the apo B/apo A1 ratio have been shown to be predictive of ischaemic stroke in patients with previous transient ischaemic attack.⁵
• Apo CII: activates lipoprotein lipase in capillaries, liberating fatty acids and monoglycerides from chylomicrons, with the fatty acids then passing into adipocytes or muscle.⁶
• Apo CIII: an antagonist of plasma triglyceride catabolism; increased apo C-III expression may lead to hypertriglyceridaemia and an atherogenic lipoprotein profile.⁷
• D: a protein component of high-density lipoprotein in human plasma.⁸
• E: involved in receptor recognition of intermediate density lipoprotein and chylomicron remnant by the liver:
  • In familial dysbetalipoproteinaemia, increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron and VLDL remnants because of a defect in apolipoprotein E.⁹
  • There is thought to be an association between apolipoprotein E and neurodegenerative conditions such as multiple sclerosis and Alzheimer's disease.¹⁰ Possession of an ApoE epsilon4 allele increases the risk of Alzheimer's disease developing from cognitive impairment with no dementia. It is also associated with a decrease in the age at onset of Alzheimer's disease.¹¹

Specific apolipoprotein disorders are rare but there is increasing knowledge and awareness as to the importance of apolipoproteins and their relevance to a variety of clinical disorders. Two of the most important specific apolipoprotein disorders are apoC-II deficiency and familial defective apoprotein B.

Apo-C-II deficiency

• Rare autosomal recessive hereditary disorder.
• Apolipoprotein C-II (apoC-II) activates lipoprotein lipase and so there is an overlap between lipoprotein lipase deficiency and apolipoprotein C-II deficiency.
• Deficiency of apolipoprotein C-II leads to an accumulation of chylomicrons and triglycerides.
• Xanthomas and hepatosplenomegaly are less common in apoC-II deficiency than in lipoprotein lipase deficiency.
• Diagnosis is by absence of apoC-II by protein electrophoresis.
• Mainstay of treatment is a fat-free diet.

Familial defective apoprotein B-100

• Autosomal dominant disorder involving a mutation of apo B that interferes with binding of LDL.
• Total cholesterol and LDL-cholesterol levels are raised and triglyceride levels are normal.
• Clinical presentation is very similar to familial hypercholesterolaemia. It has been estimated that up to 4% of patients with clinical familial hypercholesterolaemia may have familial defective apo B.