A change in the PCSK9, APOB and LDLR genes is associated with familial hypercholesterolemia (FH). This causes an increased risk for early heart attack and stroke from high LDL cholesterol (often called bad cholesterol).
LDLR gene change
The LDLR gene helps your cells capture LDL cholesterol from the bloodstream.
PCSK9 gene change
The PCSK9 gene help your cells break down LDL cholesterol.
APOB gene change
The APOB gene helps your LDL cholesterol be found and captured by the LDL receptor.
When these genes are changed or not working properly, high levels of blood cholesterol can clog your arteries and lead to health concerns, such as heart disease, heart attack and stroke. With proper medication treatment, including healthy lifestyle behaviors, you can reduce your risk to develop these health concerns.
Understanding your risk
Most individuals with two FH gene changes experience severe coronary artery disease by their mid-20s. However, this is fairly rare, at a rate of only 1 in 250,000 people.
Living with FH
Your healthcare provider can provide personalized management plan to try to reduce your chance of a future heart attack or stroke. Plans for people with these genetic changes can involve:
- Checking for high cholesterol, which should start in early childhood for anyone at risk to have FH (as young as age 2)
- Aggressive treatment to lower high cholesterol (for example, using medications such as statins)
- Control of other risk factors for heart diseases like high blood pressure and diabetes
- Healthy habits, such as a heart-healthy diet, regular exercise, weight control and not smoking
- Medical tests to look for existing heart or blood vessel disease
What does this mean for my family?
Family members related by blood may have the same genetic change. Your children and siblings have a 50 percent chance to have the same genetic change. Distant relatives may also be at risk. Genetic testing can be done for the specific gene change identified and results can be used to guide care.
In a few families, there may be two FH-related gene variants in one person, one inherited from each parent. This causes more severe FH (called homozygous FH).
At-risk family members can learn if they have the same genetic risk from a simple genetic test. Those who do not have the variant will not develop FH. A genetic counselor or doctor can help to arrange for testing. Most insurance companies will pay for this testing.
FH and pregnancy
Some LDL-lowering drugs can be harmful in pregnancy. Some medications should be stopped when a pregnancy is planned or as soon as possible after pregnancy is recognized. The safest plan is to stop the below statin drugs at least four weeks before becoming pregnant. If you become pregnant while taking one of the medications listed, talk with your healthcare provider right away because other lipid-lowering drugs may be considered:
- Rosuvastatin (Crestor)
- Atorvastatin (Lipitor)
- Simvastatin (Zocor)
- Pravastatin (Pravachol)
- Lovastatin (Altoprev, Mevacor)
- Fluvastatin (Lescol, Lescol XL)
- Pitavastatin (Livalo)
If you are taking Ezetimibe (Zetia), niacin or vitamin B3 (Niaspan, Slo-Niacin, Niacor, Niacinol, Nicotinex) and are planning to become pregnant, are pregnant or breastfeeding it is important that you talk with your healthcare provider about whether to continue them.
The Familial Hypercholesterolemia Foundation: A patient-centered non-profit foundation that is dedicated to research, advocacy and education of all forms of FH.
The National Society of Genetic Counselors “Find a Genetic Counselor Tool”: This website can help you find a genetic counselor in your area.
The American College of Medical Genetics and Genomics: This website can provide a list of geneticists in your area to help with diagnosis and treatment.
The Foundation of the National Lipid Association: Supports education, research and community outreach related to cholesterol.
American Heart Association: As an organization dedicated to fighting heart disease and stroke, this website contains information for patients and health care providers.
Genetics Home Reference: This website provides information about the effects of genetic variation on human health.
Familial Hypercholesterolemia: Screening, diagnosis and management of pediatric and adult patients: An executive summary providing clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia lipid.org/sites/default/files/articles/familial_hypercholesterolemia_1.pdf
National Lipid Association: This web site contains information aimed to enhance the practice of lipid management in clinical medicine. lipid.org
American Heart Association: A web site dedicated to heart health, with a portfolio of content dedicated to the cardiovascular and stroke professional. heart.org/HEARTORG/Professional/Professional_UCM_001093_SubHomePage.jsp
Gene Reviews - Familial Hypercholesterolemia: This Gene Review provides a detailed description of FH, including the clinical characteristics, diagnosis and testing, genetic counseling, surveillance and medical management. ncbi.nlm.nih.gov/books/NBK174884/
Clinical Genome Resource: ClinGen is an NIH-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research. search.clinicalgenome.org/kb/home?utf8=â&term=APOB
Online Mendelian Inheritance in Man® (OMIM): OMIM is a comprehensive, authoritative compendium of human genes and genetic phenotypes that is updated daily. omim.org/entry/107730?search=APOB&highlight=APOB
Find a provider
If you have these genetic variants, you may be referred to:
- A lipid specialist or clinician with expertise in FH (often through cardiology)
- A medical genetics and/or genetic counseling consultation
If you have children, they can have genetic testing for their specific variant in order to know whether they inherited the risk for FH or not. Their cholesterol levels should also be checked when they are as young as 2 years old. They should see a lipid specialist if their cholesterol levels are high.