A NOVEL LOSS OF FUCTION MUTATION OF PCSK9 GENE IN CAUCASIANS WITH LOW PLASMA LDL-CHOLESTEROL

GENETIC HETEROGENEITY OF SEVERE HYPOBETALIPOPROTEINEMIA

Comparison of two polygenic risk score to identify non-monogenic primary hypocholesterolemias in a large cohort of Italian hypocholesterolemic subjects: Polygenic hypocholesterolemias

Background: Primary Hypobetalipoproteinemias (HBL) are a group of dominant and recessive monogenic genetic disorders caused by mutations in APOB, PCSK9, ANGPTL3, MTTP, Sar1b genes and characterized by plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5th percentile of the distribution in a given population. Mutations in the candidate genes account only for a small proportion of subjects with HBL suggesting a role for a polygenic contribution to the low cholesterol phenotype. Objective: To explore the complex genetic architecture of HBL we compared two polygenic risk scores in order to assess the role of the polygenic b…