Apolipoproteins

Apolipoprotein test is used to evaluate the risk of atherogenic heart and peripheral vascular diseases. These levels may be better indicators of atherogenic risks than high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very-low-density lipoprotein [VLDL].

 

Apoproteins are the protein part of lipoproteins (such as HDL, LDL). In general, apolipoproteins play an important role in lipid transport. They act as activators to encourage the attachment of lipoproteins to lipoprotein receptors in tissue cells to allow transfer of lipoproteins (carrying fat products) into the cell. Furthermore, apolipoproteins are enzymes related to the lipoprotein synthesis. Apolipoproteins are mostly formed in the liver and intestine. The amounts of fat a person consume are the primary regulator that affect the Apolipoprotein Synthesis in the Intestine. Synthesis of Apolipoprotein in the liver is however affected by several factors in addition to the fat amounts an individual consume. Apolipoproteen synthesis in the liver is affected by the levels of several hormones including Insulin, Glucagon, Thyroxin, Estrogens, and Androgens. In addition to fat intake, alcohol consumption affect the synthesis of Apolipoprotein in the liver. The process is also affected by taking drugs like Statins, Niacin, or FIbric Acids. Quantification of apolipoproteins is used as risk factors of atherogenic disease. Still, unsolved methodologic problems within apolipoprotein immunoassays produce significant variability. There are at least nine types of apolipoprotein, including apo A-I, apo B, and apo E.

 

Apolipoprotein A (Apo A) is the major polypeptide component of HDL. Apo A has two major forms: apo A-I, which constitutes about 75% of the apo A in HDL, and apo A-II, which constitutes about 20% of the total HDL protein. Like the HDL content of the serum, apo A-I values are also higher in women than in men. Low levels of Apo A are associated with increased risk of coronary artery disease (CAD). Therefore apo A-I is used as a risk factor for atherogenic vascular disease.

 

Apolipoprotein B (Apo B) is the major polypeptide component of LDL and makes up about 80% of that protein. Forty percent of the protein portion of VLDL is composed of apo B. Apo B has been shown to exist in two forms: apo B-100 and apo B-48. Apo B-100 is synthesized in the liver and found in lipoproteins of endogenous origin (VLDL and LDL). Apo B-100 has an affinity for the LDL receptor located on cell surfaces in peripheral tissues and is involved with cellular deposition of cholesterol. Because of this, some believe that apo B-100 is an indicator of atherosclerotic heart disease. 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. Familial defective apoprotein B-100 is an 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.

 

Lp(a) (referred to as “lipoprotein little a”) is another lipoprotein. The two polypeptide components of Lp(a) are apo(a) and a LDL-like protein. An increased level of Lp(a) may be an independent risk factor for atherosclerosis and is particularly harmful to the endothelium. It has been shown that apo(a) is a deformed relative of plasminogen, which is responsible for dissolving fibrin clots. This strong resemblance between apolipoprotein and plasminogen may provide a link between lipids, the clotting mechanism, and atherogenesis. Microthrombi containing fibrin on the vessel wall become incorporated into the atherosclerotic plaque. Familial hypercholesterolemia, some forms of renal failure, nephrotic syndrome, and estrogen depletion in women over the age of 50 years may also be associated with increased levels of Lp(a).

 

Apolipoprotein C (Apo C) comprises composes a large part of VLDL. There are 3 types of apo C, called C1, C2, and C3. These are associated with hyperlipidemias. Apo-C-II deficiency is a rare autosomal recessive hereditary disorder that leads to an accumulation of chylomicrons and triglycerides. Apo C deficiency is also associated with Tangier disease and nephrotic syndrome.

 

Apolipoprotein E (Apo E) is also involved in cholesterol transport. Through genotyping, three alleles for apo E have been identified: E2, E3, and E4. Each person gets an allele from each parent. E3/3 is the normal. E2/2 is found rarely and is associated with Type III hyperlipidemia. E4/4 or 4/3 is associated with high LDL levels. The apo E4 gene has been proposed as a risk factor for Alzheimer disease.

 

The E4 allele of apo E is strongly associated with Alzheimer Disease in the general population. It is not clear how apo E functions as a risk factor modifying the age of onset in Alzheimer Disease. Apo E is found in the Neuritic Amyloid Plaques. Because Apo E can bind with Tau protein, it is believed that it can also play a role in the formation of the Neurofibrillary Tangle.

 

 

 

Normal Apolipoprotein A-I Levels

Newborns have the lowest Normal Apo A-I Levels if compared to other age groups. Apo A-I Normal Levels increase as individuals grow in age. Males tend to have higher Normal Apo A-I Levels than females at young ages. However, adolescent females start to have higher Apo A-I levels as they grow which cause adult female Apo A-I levels to normally exceed the adult male levels. The following is a listing of Normal Apo A-I Levels ranges for both males and females at different ages:

 

Newborn:

Male: 41-93 mg/dL.

Female: 38-106 mg/dL.

 

Infants and Children (6 months to 4 years):

Male: 67-167 mg/dL.

Female: 60-148 mg/dL.

 

Children and Adolescents (5 to 17 years): 83-151 mg/dL,

 

Adults:

Male: 75-160 mg/dL.

Female: 80-175 mg/dL.

 

 

Normal Apolipoprotein B Levels

Like Apo A-I, Normal Apo B Levels are the lowest in newborns compared to other age groups. Unlike Apo A-1, adolescent and adult males tend to normally have higher Apo B levels than females. The following is a listing of Normal Apolipoprotein B Levels for each age group:

 

Newborns: 11-31 mg/dL.

 

Infants and Children (6 months to 3 years): 23-75 mg/dL.

 

Children and Adolescents (5-17 years):

Male: 47-139 mg/dL.

Female: 41-132 mg/dL.

 

Adult:

Male: 50-125 mg/dL.

Female: 45-120 mg/dL.

 

Normal Apo A-I/Apo B Ratio

Male: 0.85-2.24

Female: 0.76-3.23

Normal Lipoprotein (a) Levels

Most of African-Americans normally have higher (approximately the double) Lp(a) levels than Caucasians. The following is a listing of the Normal Lp(a) Levels of both races:

 

 

Caucasians (5th to 95th percentile):

Male: 2.2-49.4 mg/dL.

Female: 2.1-57.3 mg/dL.

 

African-Americans (5th to 95th percentile):

Male: 4.6-71.8 mg/dL.

Female: 4.4-75 mg/dL.

 

 

 

Causes of Apo A-I False Indicatons

  • Physical exercise may increase Apo A-I levels.
  • Smoking may decrease Apo A-I levels.
  • Diets high in carbohydrates or polyunsaturated fats may decrease Apo A-I levels.
  • Drugs that may increase Apo A-I levels include Carbamazepine, Estrogens, Ethanol, Lovastatin, Niacin, Oral Contraceptives, Phenobarbital, Pravastatin, and Simvastatin.
  • Drugs that may decrease apo A-I levels include Androgens, Beta blockers, Diuretics, and Progestins.

 

 

 

Causes of Apo B False Indications

  • Diets high in saturated fats and cholesterol may increase Apo B levels.
  • Drugs that may increase Apo B levels include Androgens, Beta blockers, Diuretics, Ethanol, and Progestins.
  • Drugs that may decrease apo B levels include Cholestyramine, Estrogen (postmenopausal women), Lovastatin, Neomycin, Niacin, Simvastatin, and Thyroxine.

 

 

 

Drugs that affect Lipoprotein (a) Levels

The following drugs may decrease Lp(a):

  • Estrogens.
  • Neomycin.
  • Niacin.
  • Stanozolol.

 

 

 

Causes of High Apolipoprotein A-1 Levels

  • Familial Hyperalphalipoproteinemia.
  • Pregnancy.
  • Weight Reduction.

 

 

 

Causes of Low Apolipoprotein A-1 Levels

  • Coronary Artery Disease (CAD).
  • Ischemic Coronary Disease.
  • Myocardial Infarction (MI).
  • Familial Hypoalphalipoproteinemia.
  • Fish Eye Disease.
  • Uncontrolled Diabetes Mellitus.
  • Tangier Disease.
  • Nephrotic Syndrome.
  • Chronic Renal Failure.
  • Cholestasis.
  • Hemodialysis.

 

 

 

Causes of High Apolipoprotein B Levels

  • Hyperlipoproteinemia (types IIa, IIb, IV, V).
  • Nephrotic syndrome.
  • Pregnancy.
  • Hemodialysis.
  • Biliary Obstruction.
  • Coronary Artery Disease (CAD).
  • Diabetes.
  • Hypothyroidism.
  • Anorexia Nervosa Renal Failure.

 

 

 

Causes of Low Apolipoprotein B Levels

  • Tangier Disease.
  • Hyperthyroidism.
  • Inflammatory Joint Disease.
  • Malnutrition .
  • Chronic Pulmonary Disease.
  • Weight Reduction.
  • Chronic Anemia.
  • Reye Syndrome.

 

 

 

Causes of High Lipoprotein (a) Levels

  • Premature Coronary Artery Disease (CAD).
  • Stenosis of Cerebral Arteries.
  • Uncontrolled Diabetes Mellitus.
  • Severe Hypothyroidism.
  • Familial Hypercholesterolemis.
  • Chronic Renal Failure.
  • Estrogen Depletion.

 

 

 

Causes of Low Lipoprotein (a) Levels

  • Alcoholism.
  • Malnutrition.
  • Chronic Hepatocellular Disease.

 

 

 

Indication of Apo E-4 Gene

  •  Alzheimer Disease.