Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins
Abstract 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 associa...
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Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-12432-6 |
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| author | Sabina Ugovšek Andreja Rehberger Likozar Tina Levstek Katarina Trebušak Podkrajšek Janja Zupan Slobodan Antonić Miran Šebeštjen |
| author_facet | Sabina Ugovšek Andreja Rehberger Likozar Tina Levstek Katarina Trebušak Podkrajšek Janja Zupan Slobodan Antonić Miran Šebeštjen |
| author_sort | Sabina Ugovšek |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-3b0332fcd883432d93a4925bee6aba2b |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3b0332fcd883432d93a4925bee6aba2b2025-08-20T03:04:39ZengNature PortfolioScientific Reports2045-23222025-07-0115111110.1038/s41598-025-12432-6Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statinsSabina Ugovšek0Andreja Rehberger Likozar1Tina Levstek2Katarina Trebušak Podkrajšek3Janja Zupan4Slobodan Antonić5Miran Šebeštjen6Faculty of Medicine, University of LjubljanaDepartment of Vascular Diseases, University Medical Centre LjubljanaLaboratory for Translational Medical Biochemistry, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of LjubljanaLaboratory for Translational Medical Biochemistry, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of LjubljanaFaculty of Pharmacy, University of LjubljanaDepartment of Neurology, University Medical Centre LjubljanaDepartment of Cardiology, University Medical Centre LjubljanaAbstract 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.https://doi.org/10.1038/s41598-025-12432-6PCSK9 polymorphismsLipoprotein(a)Endothelial dysfunctionTotal PCSK9 levels |
| spellingShingle | Sabina Ugovšek Andreja Rehberger Likozar Tina Levstek Katarina Trebušak Podkrajšek Janja Zupan Slobodan Antonić Miran Šebeštjen Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins Scientific Reports PCSK9 polymorphisms Lipoprotein(a) Endothelial dysfunction Total PCSK9 levels |
| title | Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins |
| title_full | Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins |
| title_fullStr | Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins |
| title_full_unstemmed | Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins |
| title_short | Gain of function variants in PCSK9 gene in high risk patients after myocardial infarction with increased lipoprotein (a) values and treated with statins |
| title_sort | gain of function variants in pcsk9 gene in high risk patients after myocardial infarction with increased lipoprotein a values and treated with statins |
| topic | PCSK9 polymorphisms Lipoprotein(a) Endothelial dysfunction Total PCSK9 levels |
| url | https://doi.org/10.1038/s41598-025-12432-6 |
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