Familial hypercholesterolemia (FH) is an autosomal codominant single gene disorder caused by mutations in the LDL receptor gene (LDLR) that disrupt the normal clearance of LDL particles from the plasma. Heterozygous patients (HeFH) present a two- to three-fold raise in plasma LDL-cholesterol (LDL-C) concentrations and coronary artery disease occurs earlier among HeFH carrying negative-receptor (NR) mutations as compared with HeFH subjects carrying defective-receptor (DR) variants. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL-C levels by binding to LDLR and by enhancing its intracellular degradation.

The objective of this study is to examine to what extent variations in LDL-C and Lipoprotein (Lp) (a) concentrations are related to PCSK9 levels in a large French-Canadian cohort of HeFH subjects.

The primary hypothesis is that that PCSK9 levels have a significant impact on LDL-C concentration variability and are associated with Lp(a) levels.

Inclusion Criteria:

Subjects with familial hypercholesterolemia:

• Aged between 18-65 years
• Carrier of a mutation in the LDL receptor gene

Controls:

• Aged between 18-60 years
• HDL-cholesterol > 1.1 mmol/L
• Triglycerides < 1.7 mmol/L
• Fasting blood glucose <6.1 mmol/L
• Normal blood pressure (<130/85)

Exclusion Criteria:

• Subjects with a previous history of cardiovascular disease
• Subjects with Type 2 diabetes
• Were pregnant or nursing;
• Subjects with a history of cancer
• Subjects with acute liver disease, hepatic dysfunction, or persistent elevations of serum transaminases
• Subjects with a secondary hyperlipidemia due to any cause
• History of alcohol or drug abuse within the past 2 years
• hormonal treatment
• Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study

community sample