Margus Viigimaa*, Silver Heinsar, Dragan Lovic, Alexandra Katsimardou, Alexia Piperidou and Davit Duishvili Pages 3599 - 3604 ( 6 )
Background: Familial Hypercholesterolaemia (FH) is an autosomal-dominant genetic disease and represents the most common genetic disorder: heterozygous 1/250 births, homozygous 1/300, 000 births. FH is characterized by high to very high low-density lipoprotein cholesterol (LDL-C), which is the main cause of increased incidence of premature atherosclerotic Cardiovascular Disease (CVD) or aortic stenosis.
Objective: The aim of the review was to investigate the pathogenesis and the pathophysiology of FH.
Results: The most common (60-80%) FH cause is mutations of the LDL Receptor (LDLR) protein (6 classes with a different number of receptors and functionality). Moreover, mutations in apolipoprotein B (APOB) (<5%) and gain-of-function mutations of proprotein convertase subtilisin/kexin type 9 genes (PCSK9) (<1%) contribute to its pathogenesis. An Autosomal Recessive Hypercholesterolaemia (ARH) is another cause, very rare (1/2.500 births), mainly in Sardinia. The remaining patients with a clinical diagnosis of monogenic hypercholesterolaemia do not present any known genetic cause. Since FH is a significant public health problem, early diagnosis and treatment are of utmost importance. Recent studies demonstrated the influence of the LDLR mutation type in the FH phenotype, associating a more severe clinical phenotype and worse advanced CVD in patients with null mutation than those with receptor-defective mutations. This analysis completes the adequate clinical diagnosis.
Conclusion: Both homozygous and heterozygous FH are related to mutations of LDLR (mainly), APOB, PCSK9, while other rare forms exist. All aberrations lead to the impaired removal of LDL-C from the blood leading to its accumulation and subsequent CVD earlier than in the general population.
Familial hypercholesterolaemia, pathogenesis, pathophysiology, LDL receptor, apolipoprotein B, PCSK9, autosomal recessive hypercholesterolaemia.
Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia; Institute of Health Technologies, Tallinn University of Technology, Tallinn, Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia; Institute of Health Technologies, Tallinn University of Technology, Tallinn, Clinic for Internal Medicine InterMedica, Cardiology Department, Nis, 2nd Prop Department of Internal Medicine, Aristotle University, Thessaloniki, 2nd Prop Department of Internal Medicine, Aristotle University, Thessaloniki, Centre of Cardiology, North Estonia Medical Centre, Tallinn, Estonia; Institute of Health Technologies, Tallinn University of Technology, Tallinn