Molecular Genetic of Familial Hypercholesterolemia and Personalized Medicine

Cardiovascular disease(CVD) is one of the leading causes of death worldwide(1). Risk factors for CVD can be environmental and genetic. Family Hypercholesterolemia(FH) is a genetic factor with a dominant autosomal inheritance pattern resulting from high levels of low-density lipoprotein cholesterol (LDL) and increases the risk of premature cardiovascular disease(2). The disease, which is the most common genetic disease in the world(3), is due to a deficiency in the cholesterol recovery cycle using the conventional mechanisms of LDLR(4). FH can be monogenic or polygenic(5). Most FH-induced single-gene causes are mutations in one of the three LDLR, APOB, and PSCK9 genes, of which about 90% are generated in the LDLR gene(6). In more than 80% of cases, the FH clinical diagnosis without mutations in these genes is polygenic.DNA testing confirms FH diagnosis and helps identify at-risk relatives at an early age(5). But a negative genetic test does not deny FH diagnosis, especially when there is strong clinical phenotypic evidence(7). Despite genetic mutations known as a subset of this disorder and the availability of the commercial gene panel, the genetic testing for high costs is not normally performed in clinical care (8), FH is a complete example of personal medicine.If it is diagnosed at appropriate times, Largely prevented from the harmful consequences of the disease. On the other hand, the vital role of FH patients in the discovery of PCSK9 as a factor in the development of this disease, and as a result of the development of PCSK9 inhibitors, can be mentioned.Therefore, the participation of individuals is essential for development the drug (7).