The Genetics of FH

This gene codes for two proteins that carry digested fats and fat-like substances (such as cholesterol) from the intestine into the blood. This then allows for cholesterol to be used by the cell, stored, or removed from the body.

At least five mutations of the APOB gene have been found to be the culprit of FH.

Location: Chromosome 2, position 24.1

This gene codes for a protein that binds to low-density lipoproteins-- the primary carriers of cholesterol in the blood, which work very similarly to the APOB gene described above. LDLRs play a crucial role in regulating the amount of cholesterol in the blood, mediating endocytosis of LDL-C.

Over 1,000 mutations have been identified to contribute to FH. Some of these mutations reduce the number of LDLRs, where others disrupt the efficiency of the receptors.

Location: Chromosome 19, Position 13.2

This gene works almost exactly like the LDLR gene, except its primary job is to move the receptors that are attached to an LDL from the cell's exterior to the interior. This is because once cholesterol is inside the cell, it is able to be used by it, stored, or removed from the body.

Over ten mutations in this gene have shown to cause FH, and tend to cause an abnormally small, nonfunctional version of the LDLRAP1 protein.

Location: Chromosome 1, Position 36.11

This gene controls the number of LDL receptors that play a critical role in regulating blood cholesterol levels. The PCSK9 protein controls these levels by breaking down LDLRs before they reach the cell surface.

Several mutations of this gene have been found to cause FH. Most of these mutations enhance the activity of the PCSK9 protein, which reduces the number of LDLRs. Because of this, cholesterol remains on the outside of the cell, and cannot be brought inside for usage, storage, or removal.

Location: Chromosome 1, Position 32.3