We have over 20,000 different genes in the body. These genes are like instruction manuals for how to build a protein, and each protein has an important function that helps to keep our body working how it should. The APOB gene makes a protein called apolipoprotein B. Apolipoprotein B proteins perform many jobs in the body, including helping to carry fat and cholesterol from our intestines into our bloodstream. It also helps to attach cholesterol to LDL receptors (made by the LDLR gene) on our cells, which bring cholesterol into the cells where it can be used, stored, or gotten rid of. This process or removing excess cholesterol happens primarily in the liver.
The amount of the apolipoprotein B protein that is in the body determines how well the cholesterol can attach to the the LDL receptors. If someone has a harmful error (called a pathogenic variant) in one of their APOB genes, then their body is not going to make enough of the apolipoprotein B protein as it should. If there is not enough apolipoprotein B, then the cholesterol cannot be captured and processed as easily by the cells. This can lead to the cholesterol building up in the body, which can cause the signs and symptoms we associated with familial hypercholesterolemia.
Pathogenic variants in the APOB gene are passed through a family in an autosomal dominant pattern, meaning that anyone who carries the variant has a 50% chance to pass it down to any children they have. Women and men both have the APOB gene and have the same chances to inherit and pass down pathogenic variants. Almost all people who have a pathogenic variant in the APOB gene have a parent who also carries it.
Genetic testing for pathogenic variants in APOB is currently available, but there are a few different ways to approach testing: