Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder of lipid
metabolism, associated with elevated levels of low-density lipoprotein-cholesterol (LDLC), which
can lead to premature cardiovascular disease and early death. Early diagnosis and initiation of
treatment is important to prevent morbidity and mortality. Autosomal dominant
hypercholesterolemia (ADH) is largely due to mutations in the low-density lipoprotein receptor
gene (LDLR), the apolipoprotein B-100 gene (APOB), or the proprotein convertase subtilisin/kexin
type 9 (PCSK9). In this study, genomic DNA of unrelated Libyan individuals with clinically
diagnosed (FH) was analyzed by direct sequencing after dependent specific PCR primers
amplification and DNA purification. That led to the identification of PCSK9 gene mutations for
the first time in Libyan population which was compare to other populations. All 12 exons of
PCSK9 gene and boundaries genotyped polymorphisms were sequenced, including leucine repeats
coded in exon 1, by fluorescently tagged markers. We identified an allele for the rs67610340
polymorphism: an in-frame deletion, c.61_63delCTG (L8). We also identified another allele
rs67610340 polymorphism: an in frame insertion c.61_63InsCTG (L10). The insertion and
deletion alleles were both in exon 1 and could be associated with a risk and severity of coronary
artery disease (CAD), suggesting a direct effect of PCSK9 on atherogenesis.
Keywords: atherosclerosis, CVS, cholesterol, lipoproteins, proprotein convertases, Libya