Approximately 20% to 40% of clinically defined familial hypercholesterolemia (FH) cases do not show a causative mutation in candidate genes (mutation-negative FH), and some of them may have a polygenic origin.
The aim of this work was to study the association of SNVs in APOB, APOE, LDLR, NR5A2, PCSK9, PPARGC1A and SREBF2 genes in mutation-negative FH, with hepatic synthesis of cholesterol (desmosterol concentrations) and thus studied variants could explain in part the mechanism of hypercholesterolemia.

We studied 40 SNVs in APOB, APOE, LDLR, NR5A2, PCSK9, PPARGC1A and SREBF2 genes in 200 mutation-negative FH and 96 controls. Surrogate markers of cholesterol hepatic synthesis (desmosterol and lanosterol) were quantified by high-performance liquid chromatography-tandem mass spectrometry in both studied groups.

We observed significantly higher concentration of desmosterol in mutation-negative FH than in controls (p<0,001). There was association between 22 SNVs and desmosterol concentrantions (Table 1). All of these associated SNVs were located in 3´UTR and 5´UTR regions. These SNVs are also related with some MicroRNAs (Table 1).

There is association between 22 SNVs in APOB, APOE, LDLR, NR5A2, PCSK9, PPARGC1A and SREBF2 genes, located in 3´UTR and 5´UTR regions, and desmosterol concentrations in patients with mutation-negative FH

07 - ASSOCIATION BETWEEN SNVS IN APOB, APOE, LDLR, NR5A2, PCSK9, PPARGC1A AND SREBF2 GENES WITH DESMOSTEROL CONCENTRATIONS IN PATIENTS WITH HYPERCHOLESTEROLEMIA WITHOUT MUTATIONS IN CANDIDATE GENES