Lipoprotein (a) contributes to non-monogenic Familial Hypercholesterolemia status?

HELMAN, LORENA; GÓMEZ, ANDREA; TOSCANINI, ULISES; GIUNTA GUSTAVO; CUNIBERTI LUIS ALBERTO

Rosario

Congreso; REUNION ANUAL SAFIS 2019; 2019

SOCIEDAD ARGENTINA DE FISIOLOGIA

Introduction: Among traditionally coronary risk factors, high levels of Lipoprotein (a) (Lp(a)) represent a disorder associated with major risk of coronary artery disease in patients with clinical diagnosis of familial hypercholesterolemia (FH) and in general population. FH is an autosomal dominant genetic disorder of lipoprotein metabolism, mainly associated with the presence of mutation in three conventional genes (low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9)), characterized by elevated plasma concentration of low-density lipoprotein cholesterol (c-LDL), presence of tendon xanthomas, and it is associated with early cardiovascular disease.Aim: We aimed to analyze the measures of Lp (a) in a cohort of patients with clinical diagnosis of Familial hypercholesterolemia whom had been tested for monogenic disorder.Material and Methods: We have evaluated 38 patients with clinical diagnosis of familial hypercholesterolemia. Mutations screening were done using Sanger sequencing in the coding region and adjacent intronic areas of LDLR and PCSK9 genes and exon 26 of APOB gene. Lp(a) levels were determinated by a turbidimetric method using inmunoglobuling G anti-human Lp(a) (Quantia Lp(a) 7K00-01) in an Architect autoanalyzer C16000 (Abbott Diagnostics) and elevated Lp(a) was defined as levels > 50 mg/dL. Results: The thirty nine point five percent of the analyzed patients did not have pathogenic mutations in coding region and adjacent intronic areas of LDLR, PCSK9 neither in exon 26 of APOB gene. On the other hand, they exhibited higher levels of Lp(a) (at least twofold, p=0,02) in comparison with the group of patients with a monogenic disorder probed. Conclusions: We concluded that when the monogenic disorder is not present in patients with clinical diagnosis of FH, high levels of serum Lp(a) could be indicative of polygenic or oligogenic cause. Screening for LPA gene variants, such as the kringle IV type 2 (KIV-2) copy number variants would be interesting to elucidate in future analyses.