What Are the Genetic Causes of Familial Hypercholesterolemia?

What Are the Genetic Causes of Familial Hypercholesterolemia?

Familial hypercholesterolemia is the high level of LDL (low-density lipoprotein) cholesterol. It causes plaque formation in the vessels at an early age and increases the risk of cardiovascular diseases. It can manifest itself with symptoms such as heart attack, chest pain, and stroke in patients. It is seen in one of 250 people on average.

Who should be suspected?

  • High serum cholesterol levels (LDL or non-HDL cholesterol)
  • Cardiovascular disease at an early age (<55 years in men, <65 years in women)
  • Xanthoma
  • Corneal arch (<45 years)
  • Xanthelasma
  • Family history of hypercholesterolemia
  • Family history of coronary artery disease <55 years in men and <65 years in women

Familial hypercholesterolemia genetics

LDLR, APOB, LDLRAP1, PCSK9 genes are involved in LDL metabolism and approximately 60% of patients have mutations in these genes. These mutations (errors) cause elevated serum LDL and total cholesterol levels.


Genetic testing helps the diagnosis by showing the specific mutation in cases of hypercholesterolemia (especially with a family history).

  • Early diagnosis enables early treatment.
  • Early treatment and follow-up reduce plaque formation and complications.
  • The risky individuals in the family are screened and benefit from the chance of early treatment.