Reasons For Testing

People take this test for a variety of reasons. Some want to know their genetic risk for FH as testing may lead to changes in the management of high cholesterol. Others want to help their family members understand their risk.

kit
  • Must be over age 18.
  • Cannot have had a bone marrow transplant.
  • Must have high cholesterol and know your cholesterol levels.
    • If 18-25 years of age, LDL must be 155 or higher.
    • If over age 25, LDL must be over 190.
  • Testing is particularly important for anyone with high cholesterol and a parent, sibling or child who also has high cholesterol or with premature heart disease.
Order $290

About Familial Hypercholesterolemia (FH)

What is FH?

Hypercholesterolemia is a term that means having high levels of cholesterol in your blood. Cholesterol is a waxy substance found in all the cells of your body. Cholesterol can build up in blood vessels and damage them; this is known as atherosclerosis. Having high blood cholesterol raises the risk for heart disease, the leading cause of death, and for stroke, the fifth leading cause of death in the US.

Sometimes, high cholesterol is caused by genetic variants found in a person’s DNA. These variants may have been inherited from one or both of your parents and can be passed along to your children and grandchildren. Familial is a term that refers to a condition inherited, or passed down through generations of a family. Therefore, the term Familial Hypercholesterolemia (FH) refers to high cholesterol that runs in a family.

Symptoms of high cholesterol are not always obvious. Many affected people are unaware that their cholesterol is too high.

There are two types of cholesterol: low-density lipoprotein (LDL) cholesterol, often called “bad” cholesterol and high-density lipoprotein (HDL) cholesterol, often called “good” cholesterol. Your body requires certain amounts of both types of cholesterol, but too much “bad” cholesterol or not enough “good” cholesterol can lead to atherosclerosis and increase the risk of heart disease and stroke. The following table shows LDL cholesterol levels that are considered high (Hopkins et al. 2011. PubMed ID: 21600530).

Age (in years) LDL Cholesterol (mg/dL)
< 20 > 190
20 - 29 > 220
> 30 > 250

How is FH inherited?

Dominant
Dominant

Most FH cases are dominant which means only one gene variant is needed to cause FH. DNA variants in APOB, LDLR, and PCSK9 are dominant. In this case, parents and children would each have a 1 in 2 (50%) chance of having the same DNA variant.

Recessive
Recessive

DNA variants in LDLRAP1 are recessive. This means 2 variants (one from each parent) are needed to cause FH. When both parents have one DNA variant in LDLRAP1, each child has a 1 in 4 (25%) chance of having both variants.

Approximately one in every six adults in the United States has high cholesterol (CDC: High serum total cholesterol—an indicator for monitoring cholesterol lowering efforts; U.S. adults, 2005–2006. www.cdc.gov/nchs/data/databriefs/db02.pdf)

A person with a variant in the LDLR, APOB, PCSK9, or LDLRAP1 genes has a 1 in 2 (50%) chance of passing the variant to each of their children.
People with two variants in these genes have a 3 in 4 (75%) chance of passing one of the causative variants to their children.

Genetic Testing For FH

Why get genetic testing for FH?

Genetic testing is important for people with high cholesterol because it might help you understand the cause of your high cholesterol. This would help you and your doctor set an appropriate treatment plan.

Genetic testing can also help identify family members who are at risk.

What is genetic testing?

Genetic testing is the process by which we isolate and test DNA from a patient’s saliva sample. Within DNA, we look at a person’s genes. Genes are instructions to tell our bodies how to build, maintain, and function throughout our lives. Genetic testing looks carefully at certain genes to determine if the instructions are not written properly (variants) and are causing certain medical conditions. This information can help us diagnose or give risks for developing a disorder such as FH.

When to suspect FH:
  • If your cholesterol tests have been consistently high.
  • If you have had a heart attack at an early age or if you have a family history of high cholesterol or early onset heart disease.
  • If you have visible signs of FH such as swollen tendons or yellow “fatty” deposits in the skin.
Which genes are tested?

There are four known important genes that cause FH (LDLR, APOB, PCSK9, LDLRAP1).

Each of these genes has instructions for the body to make a certain kind of protein. Proteins made by the body are different than the proteins we eat in our diet. Proteins are made using the instructions in DNA and are important to the structure, function, and regulation of the body’s organs and tissues.

  • LDLR gene- the protein produced by this gene helps remove cholesterol from your blood. Variants in this gene are the most frequent cause of FH.
  • APOB gene- the protein produced by this gene helps transport cholesterol in your blood. Variants in this gene make it difficult for the LDLR protein to remove cholesterol from your blood.
  • PCSK9 gene- the protein produced by this gene breaks down proteins used to remove cholesterol from your blood. Variants in this gene can result in not enough of the proteins needed for proper removal of cholesterol from your blood.
  • LDLRAP1 gene- the protein produced by this gene also helps to remove cholesterol from your blood. Variants in this gene are a rare cause of FH. Two DNA variants are needed in this gene to cause FH. We will not report cases where only one DNA variant was found in this gene.

These genes do not change over the course of a person’s lifetime. However, if you test negative and the testing technology improves, you may be able to detect more variants in the future.

What can Genetic Testing for FH tell me?

Testing would help you and your doctor set an appropriate treatment plan. This test may also help identify family members who are at risk.

Negative Sample Report

A negative report means the APOB, LDLR, LDLRAP1 and PCSK9 genes were analyzed and no DNA variants known to cause FH were found. FH is the cause for only a small fraction of people with high cholesterol. There are other health and lifestyle factors that result in high cholesterol.

Since this test is designed to detect only specific types of genetic changes, this test may not detect all types of genetic changes known to cause FH. The report only includes genetic changes that are currently known or expected to cause familial hypercholesterolemia. Some people with FH may receive a negative test result because this test gives positive results for only 3 out of 4 people with FH.

It is recommended you share your report with your healthcare provider.

Genetic counseling is recommended to help understand what this means for you and family members and is available through PWNHealth, the independent provider network that placed your order. To schedule a phone or video consultation with a genetic counselor, please contact PWNHealth by phone: (888) 494-7333 or email: gc@pwnhealth.com.

Positive Sample Report

A positive result means a DNA variant expected to cause familial hypercholesterolemia was identified.

It is recommended you share this report with your healthcare provider as these results may lead to changes in the management of your high cholesterol.

The DNA variant found may have been inherited, and may also be present in other blood relatives, including your children. We recommend that you share this report with your family members.

Genetic counseling is recommended to help understand what this means for you and family members and is available through PWNHealth, the independent provider network that placed your order. To schedule a phone or video consultation with a genetic counselor, please contact PWNHealth by phone: (888) 494-7333 or email: gc@pwnhealth.com.

Support Available

Information about the treatment and management of high cholesterol is available through the National Lipid Association (https://www.lipid.org/).

Information about the treatment and management of FH is available through the FH Foundation (https://thefhfoundation.org/).

Genetic Counseling

Genetic counseling is recommended to help understand what this means for you and family members and is available through PWNHealth, the independent provider network that placed your order. To schedule a phone or video consultation with a genetic counselor, please contact PWNHealth by phone: (888) 494-7333 or email: gc@pwnhealth.com.