Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins

Ugovšek, Sabina (author), Rehberger Likozar, Andreja (author), Levstek, Tina (author), Trebušak Podkrajšek, Katarina (author), Zupan, Janja (author), Antonić, Slobodan (author), Šebeštjen, Miran (author)

The proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid metabolism, inflammation and haemostasis. Pathogenic gain-of-function variants in the PCSK9 gene are causative of autosomal-dominant form of familial hypercholesterolemia, while several PCSK9 alleles have been associated with elevated levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of cardiovascular disease. Elevated lipoprotein(a) (Lp(a)) levels, regardless of LDL-C levels, as well as functional and morphological changes in the arterial vessel wall predict future cardiovascular events. In our study, we aimed to identify whether treatment with statins nullifies the effect of four gain-of-function gene variants in PCSK9 on lipoproteins and arterial wall properties in high-risk post-myocardial infarction patients with severely elevated Lp(a) levels. We included 68 patients after myocardial infarction with elevated Lp(a) levels on maximal statin therapy. Biochemical analysis of lipid parameters and total PCSK9 levels were performed. Arterial wall properties were measured by ultrasound. Genotyping was performed for four gain-of-function, i.e. rs11206510, rs2479409, rs2479408 and rs1711503, and one intergenic, rs11591147 PCSK9 single nucleotide polymorphisms. The results showed no association between studied PCSK9 gene variants and lipid parameters, PCSK9 levels and arterial wall properties in our patient cohort. Clinical, biochemical and arterial wall parameters did not differ between the group with lower compared to group with higher number of PCSK9 alleles. Our results suggest that in high-risk patients after myocardial infarction with increased Lp(a) levels treated with statins the studied PCSK9 gain-of-function gene variants are associated neither with lipoproteins nor with arterial wall properties.

• Language: English
• Keywords: PCSK9 polymorphisms, lipoprotein(a), endothelial dysfunction, total PCSK9 levels
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 11 str.
• Numbering: Vol. 15, art. 26753
• PID: 20.500.12556/RUL-171412
• UDC: 616.127-005.8
• ISSN on article: 2045-2322
• DOI: 10.1038/s41598-025-12432-6
• COBISS.SI-ID: 244049155
• Publication date in RUL: 26.08.2025

Record is a part of a journal

• Title: Scientific reports
• Shortened title: Sci. rep.
• Publisher: Nature Publishing Group
• ISSN: 2045-2322
• COBISS.SI-ID: 18727432

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: polimorfizmi PCSK9, lipoprotein(a), endotelijska disfunkcija, skupne ravni PCSK9, miokardni infarkt