LDL‐cholesterol and PCSK9 in patients with familial hypercholesterolemia: influence of PCSK9 variants under lipid‐lowering therapy

Abstract Background Familial hypercholesterolemia (FH), an autosomal dominant genetic disease with the elevated levels of low‐density lipoprotein (LDL) cholesterol (LDL‐C), increases the risk of coronary artery disease (CAD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) gene is associated with FH. There is a positive relationship between circulating LDL‐C and PCSK9 levels, a potential CAD condition, without lipid‐lowering therapy (LLT); however, we do not know whether their correlation exists in FH patients under LLT. Methods This study compared the correlation of PCSK9 variants among patients with FH under LLT (n = 70; mean age, 53 years; male, 63%). LDLR, PCSK9 and APOB variants were analyzed using next‐generation sequencing. Results The LDL‐C and PCSK9 levels in patients with gain‐of‐function (GOF) variants of PCSK9 (n = 7) were mostly similar to those in patients with LDLR variants (n = 17) or variant‐negative patients (n = 46). A significant positive correlation was observed between LDL‐C and PCSK9 levels in patients with GOF variants of PCSK9 (r = 0.79, p = 0.04), but not in patients with LDLR variants or variant‐negative patients. Conclusion The LDL‐C‐PCSK9 correlation is suggested to be retained in FH patients with GOF variants of PCSK9 even under LLT, and these variants can be used as molecular markers for additional treatment with statins in FH patients.