Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values

Ugovšek, Sabina; Rehberger Likozar, Andreja; Levstek, Tina; Trebušak Podkrajšek, Katarina; Zupan, Janja; Šebeštjen, Miran

doi:10.3390/ijms25020736

Open AccessArticle

Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values

by

Sabina Ugovšek

^1,2,*

,

Andreja Rehberger Likozar

³

,

Tina Levstek

^4,5

,

Katarina Trebušak Podkrajšek

^4,5

,

Janja Zupan

⁶

and

Miran Šebeštjen

^2,3,7,*

¹

Division of Internal Medicine, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia

²

Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia

³

Department of Vascular Diseases, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia

⁴

Laboratory for Translational Medical Biochemistry, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia

⁵

Clinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre Ljubljana, Vrazov trg 1, 1000 Ljubljana, Slovenia

⁶

Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, 1000 Ljubljana, Slovenia

⁷

Department of Cardiology, University Medical Centre Ljubljana, Zaloška cesta 7, 1000 Ljubljana, Slovenia

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2024, 25(2), 736; https://doi.org/10.3390/ijms25020736

Submission received: 5 December 2023 / Revised: 20 December 2023 / Accepted: 4 January 2024 / Published: 6 January 2024

(This article belongs to the Special Issue Molecular Mechanisms and Pathophysiology of Atherosclerosis 2.0)

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Abstract

Lipoprotein(a) (Lp(a)) is an independent risk factor for future coronary events. Variants rs10455872 and rs3798220 in the gene encoding Lp(a) are associated with an increased Lp(a) concentration and risk of coronary artery disease. We aimed to determine whether in high-risk coronary artery disease patients these two genetic variants and the kringle IV type 2 (KIV-2) repeats are associated with impairment of inflammatory and hemostatic parameters. Patients after myocardial infarction with elevated Lp(a) levels were included. Blood samples underwent biochemical and genetic analyses. In carriers of the AC haplotype, the concentrations of tumor necrosis factor (TNF)-α (4.46 vs. 3.91 ng/L, p = 0.046) and plasminogen activator inhibitor-1 (PAI-1) (p = 0.026) were significantly higher compared to non-carriers. The number of KIV-2 repeats was significantly associated with the concentration of high-sensitivity C-reactive protein (ρ = 0.251, p = 0.038) and overall fibrinolytic potential (r = −0.253, p = 0.038). In our patients, a direct association between the AC haplotype and both TNF-α and PAI-1 levels was observed. Our study shows that the number of KIV-2 repeats not only affects proatherosclerotic and proinflammatory effects of Lp(a) but is also associated with its antifibrinolytic properties.

Keywords: inflammation; hemostasis; lipoprotein(a); rs10455872; rs3798220; KIV-2 repeats

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MDPI and ACS Style

Ugovšek, S.; Rehberger Likozar, A.; Levstek, T.; Trebušak Podkrajšek, K.; Zupan, J.; Šebeštjen, M. Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values. Int. J. Mol. Sci. 2024, 25, 736. https://doi.org/10.3390/ijms25020736

AMA Style

Ugovšek S, Rehberger Likozar A, Levstek T, Trebušak Podkrajšek K, Zupan J, Šebeštjen M. Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values. International Journal of Molecular Sciences. 2024; 25(2):736. https://doi.org/10.3390/ijms25020736

Chicago/Turabian Style

Ugovšek, Sabina, Andreja Rehberger Likozar, Tina Levstek, Katarina Trebušak Podkrajšek, Janja Zupan, and Miran Šebeštjen. 2024. "Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values" International Journal of Molecular Sciences 25, no. 2: 736. https://doi.org/10.3390/ijms25020736

APA Style

Ugovšek, S., Rehberger Likozar, A., Levstek, T., Trebušak Podkrajšek, K., Zupan, J., & Šebeštjen, M. (2024). Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values. International Journal of Molecular Sciences, 25(2), 736. https://doi.org/10.3390/ijms25020736

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Haplotype of the Lipoprotein(a) Gene Variants rs10455872 and rs3798220 Is Associated with Parameters of Coagulation, Fibrinolysis, and Inflammation in Patients after Myocardial Infarction and Highly Elevated Lipoprotein(a) Values

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