APOB

The APOB gene encodes apolipoprotein B [R].

APOB helps transport fats through the bloodstream and into the liver for storage, processing, or removal from the body. It also helps absorb fat-soluble vitamins (like vitamin E and vitamin A) from food [R].

Mutations in APOB may cause [R, R]:

• Familial hypercholesterolemia, a condition in which LDL cholesterol is unusually high. People with this condition are at increased risk of heart disease.
• Familial hypobetalipoproteinemia, a condition in which the body cannot absorb or transport fats or certain vitamins. People with this condition often develop fatty liver disease, fatty stools, and low growth rate.

Variants in APOB have also been linked to [R, R]:

• LDL cholesterol levels
• Lifespan
• Type 2 diabetes

The APOB gene provides instructions for making two versions of the apolipoprotein B protein, a short version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100. Both of these proteins are components of lipoproteins, which are particles that carry fats and fat-like substances (such as cholesterol) in the blood.

Apolipoprotein B-48 is produced in the intestine, where it is a building block of a type of lipoprotein called a chylomicron. As food is digested after a meal, chylomicrons are formed to carry fat and cholesterol from the intestine into the bloodstream. Chylomicrons are also necessary for the absorption of certain fat-soluble vitamins such as vitamin E and vitamin A.

Apolipoprotein B-100, which is produced in the liver, is a component of several other types of lipoproteins. Specifically, this protein is a building block of very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). These related molecules all transport fats and cholesterol in the bloodstream.

Low-density lipoproteins are the primary carriers of cholesterol in the blood. Apolipoprotein B-100 allows these particles to attach to specific receptors on the surface of cells, particularly in the liver. The receptors transport low-density lipoproteins into the cell, where they are broken down to release cholesterol. The cholesterol is then used by the cell, stored, or removed from the body.

APOB

APOB is a gene that encodes a protein called Apolipoprotein B (ApoB), which is a member of a larger class known as apolipoproteins that bind to fat molecules and form a complex of fat and protein called a lipoprotein [R]. Lipoproteins act as carriers for fats around the body [R].  ApoB is a crucial apolipoprotein of LDL or low density lipoprotein (known commonly as bad cholesterol) as well as other carrier lipoproteins VLDL (Very low density lipoprotein) and IDL (intermediate density lipoprotein), both of which can be potentially harmful like LDL [R2]. Despite the well-known correlation between high LDL levels and and risk of heart disease, concentration of ApoB molecules are considered a better gauge of risk of heart disease since one molecule of it is present in all potentially artery hardening lipoproteins, not just LDL [R2]. Therefore monitoring ApoB concentration, especially in ratio with another apolipoprotein ApoA, has become an important way to detect potential heart disease [R2].

Abnormally high levels of ApoB in the blood is defined as hypercholesterolemia, and may be the result of a mutation in the APOB gene, and in that case considered familial hypercholesterolemia [R3].

Low levels of ApoB may be the result of a genetic disorder familial hypobetalipoproteinemia (FHBL), defined when ApoB levels (or LDL concentration) are less than the 5th percentile in blood plasma [R4] also often caused by a mutation in the APOB gene.

The APOB gene produces 2 forms of protein; one called ApoB48, which is made in the small intestine and ApoB100, which is made in the liver [R5]. In the form of LDL and another apolipoprotein VLDL.

ApoB proteins can provide resistance against bacterial infection [R6].

Increased levels of ApoB may be a cause for insulin resistance [R7].

     familial hypobetalipoproteinemia More than 90 mutations in the APOB gene have been found to cause familial hypobetalipoproteinemia (FHBL), a disorder that impairs the body’s ability to absorb and transport fat. Most APOB gene mutations that cause FHBL lead to the production of apolipoprotein B that is abnormally short. The severity of the condition largely depends on the length of the abnormal apolipoprotein B. Some mutations in the APOB gene lead to the production of a protein that is shorter than apolipoprotein B-100, but longer than apolipoprotein B-48. In these cases, normal apolipoprotein B-48 is still made in the intestine. The normal-length apolipoprotein B-48 can form chylomicrons normally, but the abnormally short apolipoprotein B-100 produced in the liver is less able to produce lipoproteins. Other mutations result in a protein that is shorter than both apolipoprotein B-48 and apolipoprotein B-100. In these cases, no normal-length apolipoprotein B protein is produced. The severely shortened protein is not able to form lipoproteins in the liver or the intestine. Generally, if both versions of the protein are shorter than apolipoprotein B-48, the signs and symptoms are more severe than if some normal length apolipoprotein B-48 is produced. All of these protein changes lead to a reduction of functional apolipoprotein B. As a result, the transportation of dietary fats and cholesterol is decreased or absent. A decrease in fat transport reduces the body’s ability to absorb fats and fat-soluble vitamins from the diet, leading to the signs and symptoms of FHBL. hypercholesterolemia At least five mutations in the APOB gene are known to cause a form of inherited hypercholesterolemia called familial defective apolipoprotein B-100 (FDB). This condition is characterized by very high levels of cholesterol in the blood and an increased risk of developing heart disease. Each mutation that causes this condition changes a single protein building block (amino acid) in a critical region of apolipoprotein B-100. The altered protein prevents low-density lipoproteins from effectively binding to their receptors on the surface of cells. As a result, fewer low-density lipoproteins are removed from the blood, and cholesterol levels are much higher than normal. As the excess cholesterol circulates through the bloodstream, it is deposited abnormally in tissues such as the skin, tendons, and arteries that supply blood to the heart (coronary arteries). A buildup of cholesterol in the walls of coronary arteries greatly increases a person’s risk of having a heart attack. other disorders Researchers are studying other variations (polymorphisms) in the APOB gene that may influence heart disease risk in people without inherited cholesterol disorders. Some studies have found that certain polymorphisms are associated with higher levels of low-density lipoproteins in the blood and an increased chance of developing or dying of heart disease. Other studies, however, have not shown such an association. It is clear that a large number of genetic and lifestyle factors, many of which remain unknown, determine the risk of developing this complex condition.

     The APOB gene provides instructions for making two versions of the apolipoprotein B protein, a short version called apolipoprotein B-48 and a longer version known as apolipoprotein B-100. Both of these proteins are components of lipoproteins, which are particles that carry fats and fat-like substances (such as cholesterol) in the blood. Apolipoprotein B-48 is produced in the intestine, where it is a building block of a type of lipoprotein called a chylomicron. As food is digested after a meal, chylomicrons are formed to carry fat and cholesterol from the intestine into the bloodstream. Chylomicrons are also necessary for the absorption of certain fat-soluble vitamins such as vitamin E and vitamin A. Apolipoprotein B-100, which is produced in the liver, is a component of several other types of lipoproteins. Specifically, this protein is a building block of very low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs). These related molecules all transport fats and cholesterol in the bloodstream. Low-density lipoproteins are the primary carriers of cholesterol in the blood. Apolipoprotein B-100 allows these particles to attach to specific receptors on the surface of cells, particularly in the liver. The receptors transport low-density lipoproteins into the cell, where they are broken down to release cholesterol. The cholesterol is then used by the cell, stored, or removed from the body.

·         Diet and/or supplementation high in Omega-3 fatty acids reduce the risk of heart disease by degrading ApoB [R8].

·         Regular exercise can reduce ApoB levels [R9].

·        Vitamin E and A supplementation are necessary in combating FHBL [R10].