**2. Definition and etiology of familial hypercholesterolemia**

Familial hypercholesterolemia (FH) is a genetic and metabolic disorder that affects the metabolism of cholesterol [1–10].

Currently, the genes involved in HF are the following: low-density lipoprotein receptor (LDLR) gene, apolipoprotein B-100 (APOB) gene and proprotein convertase subtilisin kexin type 9 (PCSK9) gene, LDLR adaptor protein 1 (LDLRAP1) gene [1–10]. See **Table 1**.

The mutation in LDLR gene, APOB gene and PCSK9 gene is inherited following an autosomal dominant/autosomal co-dominant pattern and the mutation in LDLRAP1 gene is inherited following an autosomal recessive pattern [1–10].

Mutations of the genes cause defective LDL uptake and degradation, which in-turn leads to an elevation of plasma low-density lipoprotein-cholesterol (LDL-C) level, producing the hypercholesterolemia phenotype. The chronic exposure to high levels of LDL-C lead to the development of atherosclerosis and cardiovascular disease at an early age [1–10].


**Table 1.**

*Genes involved in familial hypercholesterolemia.*

Two main types of HF are distinguished: heterozygous familial hypercholesterolemia and homozygous familial hypercholesterolemia. Heterozygous familial hypercholesterolemia is usually caused by a single pathogenic variant in one of the genes associated with familial hypercholesterolemia, mostly in LDLR. Homozygous familial hypercholesterolemia is caused by biallelic pathogenic variants, generally in LDLR [1–10].
