Why Is FH Important?
In FH, LDL cholesterol is usually elevated from childhood. The earlier the diagnosis is confirmed and treatment is started, the better the lifelong risk of cardiovascular complications can be reduced.
A practical benefit of a genetic result is also cascade testing, meaning the early identification of at risk relatives.
Who Should Consider FH Testing?
Testing is particularly suitable if:
- You have had persistently high LDL cholesterol, especially from a young age, or if it responds poorly to lifestyle measures.
- There has been a heart attack, angina pectoris, stroke or sudden death at a younger age in your family.
- FH has already been diagnosed in your family.
- You have suspicious clinical signs, such as tendon xanthomas or a strong family history. These are always assessed by a doctor.
What Does the Test Examine Genetically?
FH is most commonly associated with variants in genes that affect the uptake of LDL particles:
- LDLR, APOB, PCSK9, the main genes associated with FH
The test may also include additional genetic information that helps refine overall risk assessment and treatment planning.
1) Monogenic FH, Causal Variants
Detection of known clinically significant variants, including the possibility of detecting some larger rearrangements, such as deletions or duplications in the analysed region.
2) Polygenic Risk
In some people with high LDL cholesterol, no single major causal variant is found. Instead, the condition may be influenced by the combined effect of many small genetic factors, known as polygenic risk.
Therefore, the following may be assessed:
- Polygenic risk for LDL hypercholesterolaemia
- Polygenic risk for cardiovascular disease, CVD
3) Genetics of Treatment Response, Pharmacogenetics
For selected variants, it is possible to estimate:
- A higher risk of side effects from certain statins, for example SLCO1B1
- Other factors influencing the effectiveness or choice of therapy, for example CYP2C9, APOE and ABCG2
Optional Addition: APOE and Alzheimer’s Disease Risk
If included in the selected scope of testing, the test may also detect the APOE genotype, which is associated with the risk of Alzheimer’s disease. We always recommend explaining in advance what this information means and what its limitations are.
How Is the Test Performed?
- The test is usually performed from a blood sample. Depending on the selected procedure, DNA from another suitable type of material may also be possible.
- The result includes expert interpretation and recommendations for the next steps.
Insurance Coverage: in indicated cases, the test may be performed under health insurance coverage, always depending on the clinical indication and agreement with the doctor.
How to Interpret the Result in Practice
- Positive finding of a causal variant: confirms a genetic cause of FH and is important for treatment as well as for testing relatives.
- Negative finding of causal variants: does not completely exclude FH. Other untested or very rare variants may be involved, and polygenic risk and lifestyle may also play a role.
- Increased polygenic risk: supports the explanation of polygenic hypercholesterolaemia and may help with overall risk assessment.
Method and Limitations of the Test, Briefly and Clearly
The test is based on genotyping using an SNP array, Illumina GSA_DTC. This method reliably detects a range of predefined variants and may also detect some larger rearrangements in the analysed regions.
Important limitations:
- The test typically does not detect all possible variants in the listed genes, especially completely new or very rare variants.
- The result must always be assessed in relation to lipid levels, family history and clinical findings. In some cases, targeted sequencing may be recommended.
