Familial Hypercholesterolemia: Explained

What are the Familial Hypercholesterolemia genes, and what conditions are they linked to?

The genes LDLR, APOB, PCSK9, and LDLRAP1 regulate the cholesterol levels in your body. Mutations in these are associated with Familial Hypercholesterolemia - a condition marked by elevated LDL cholesterol levels. 

So, what does it mean to have a mutation in these genes?

• It may be harder for your body to regulate and remove cholesterol from your blood. [1]

• Cholesterol levels may be normal, high, or very high in those with FH. 

• The key difference between FH and the non-genetic form of high cholesterol is that people with FH are born with higher cholesterol levels.

LDL cholesterol is involved in the build-up of plaques in the arteries. This can increase the risk of developing diseases such as coronary heart disease and stroke at a younger age. [1]

The widespread use of lipid-lowering medications makes it hard to identify FH by personal or family history. However, some classic features of FH include:

• LDL cholesterol levels of over 190 mg/dL in adults

• Family history of early heart attacks or heart disease

• Swollen or painful tendons

• Bumps around the knuckles, elbows, or knees (these can also be seen in people who do not have FH.) [1]

Why is it helpful to understand if you have variants in these genes?

If you have a mutation in one of these genes, you should speak with your healthcare provider and genetic counselor for guidance as soon as possible.

Genetic testing can be a powerful tool to help you and your provider understand your unique genetic predisposition. You can use this knowledge to work with your provider and counselor to better understand your risk. They will also consider other risk factors such as age, family history, and lifestyle factors.

By creating a plan with your provider, your risk of developing cardiovascular diseases may be reduced. This plan may include:

• More frequent screenings and check-ups

• Healthy diet and lifestyle changes 

• Using medication to lower your levels of LDL-cholesterol

• Testing at-risk family members for FH, especially children. Children started on high-potency statins by age 8-10 may have the same life expectancy as someone without FH.

A positive result is important for your entire family. It is likely some of your family also carry the genetic variant(a). Your family members may carry out testing to understand their unique risk. It is important to let your family know your results so that they can talk to their doctors to make their plans. This is particularly important for families who are planning to have children. With LetsGetChecked’s family cascade testing service, your family members can also take myGeneticScreen to help determine their risk.

Let’s recap

• Familial Hypercholesterolemia is a type of inherited disorder that can increase your levels of LDL cholesterol in the blood, which can contribute to the creation and build-up of plaques that can increase the risk of developing cardiovascular diseases at a younger age.

• If a mutation in one of the genes LDLR, APOB, PCSK9, and LDLRAP1 is found, it may be harder for your body to regulate and remove cholesterol from your blood. This means that your cholesterol levels may be higher than considered normal.

• If you have a mutation in any of the Familial Hypercholesterolemia genes, you should speak with your genetic counselor and healthcare provider for guidance on management options which may include medication.

• If left untreated, men will have a 50% risk of developing cardiovascular disease by the age of 50 and women will have a 30% risk of developing cardiovascular disease by the age of 60.

• Prevention is always better than a cure, so genetic testing can be a powerful tool to better understand your risk, together with other risk factors such as age, family history, and lifestyle factors, to minimize the risks and effects of high cholesterol.

• Any results that you receive are also very important for your entire family, and may also impact their healthcare. With LetsGetChecked’s family cascade testing service, your family members can also take myGeneticScreen to help determine their risk.

• Even with a negative result, you should continue to monitor for any changes in your general health, and attend screening appointments as recommended.