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

• Main Authors: Hamasaki, M. (Author), Hara, K. (Author), Kotani, K. (Author), Sakane, N. (Author)
• Format: Article
• Language: English
• Published: John Wiley and Sons Inc 2021
• Subjects: adult; antilipemic agent; APOB gene; Article; blood; Cholesterol, LDL; clinical effectiveness; clinical feature; colestilan; drug effect; drug efficacy; drug response; ezetimibe; familial hypercholesterolemia; female; Female; gain of function mutation; gain-of-function mutation; gene; genetic hypercholesterolemia; genetic variability; genetics; high throughput sequencing; human; Humans; Hyperlipoproteinemia Type II; Hypolipidemic Agents; LDLR gene; lipid-lowering therapy; low density lipoprotein cholesterol; low-density lipoprotein receptor; major clinical study; male; Male; middle aged; Middle Aged; mutation; Mutation; PCSK9 gene; PCSK9 inhibitor; PCSK9 protein, human; proprotein convertase 9; Proprotein Convertase 9; risk factor; statins; treatment outcome
• Online Access: View Fulltext in Publisher
• ISBN: 08878013 (ISSN)
• DOI: 10.1002/jcla.24056

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. © 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.