Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Malle, E.
The role of endogenous thrombin potential, fibrinolytic markers and their functional gene polymorphisms in the pathogenesis of central serous chorioretinopathy.
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2020. pp. 93
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Haas Anton
- Prüller Florian
- Raggam Reinhard Bernd
- Weger Martin
- Altmetrics:
- Abstract:
- Background: Central serous chorioretinopathy (CSC) is a common chorioretinal disease, characterized by choroidal hyperpermeability leading to neurosensory and/or retinal pigment epithelial detachments. Hypofibrinolysis due to higher plasma concentrations of plasminogen activator type 1 (PAI-1) or lower activity of tissue-type plasminogen activator (t-PA) has been implicated in the pathogenesis of CSC. Clotting factors, fibrinolysis markers and functional polymorphisms in the PAI-1 (SERPINE 1) and t-PA (PLAT) gene are thus potential risk factors for CSC. The aim of the present thesis was therefore to investigate a hypothesized association between endogenous thrombin potential (ETP), a global coagulation marker, t-PA antigen plasma levels and the PAI-1 4G/5G and the t-PA -7351C>T gene variants and the presence of CSC. Methods: The present dissertation includes data from two different studies. First, ETP and t-PA antigen plasma levels were investigated in 59/ 63 patients and 58 control subjects. ETP was determined with INNOVANCE® ETP (BCS® XP Coagulation System, Siemens Healthineers, Vienna, Austria), whereas t-PA antigen levels were determined with Quantikine® ELISA (R&D Systems, Inc., Minneapolis, USA). In a second step, we collected blood samples of 172 CSC patients and 313 control subjects for genotyping of the PAI-1 4G/5G and the t-PA -7351C>T polymorphisms. Genotypes of the aforementioned polymorphisms were determined by TaqManTM fluorogenic 5´-exonuclease assays (Applied Biosystems, Vienna, Austria). Results: Mean ETP levels (375.0 +- 57.2 mE vs. 367.1 +- 51.3 mE, p=0.43) did not significantly differ between patients and controls. Mean plasma t-PA antigen concentrations were significantly higher in CSC patients compared to controls (3673.1 +- 1281.6 pg/ml vs. 3228.0 +- 1079.8 pg/ml, p=0.04). Allelic frequencies or genotype distributions of neither the PAI-1 4G/5G nor the t-PA -7531C>T polymorphisms were significantly different between patients with CSC and control subjects (PAI-1 4G/4G: 24.4% vs. 20.4, p=0.36; t-PA -7351CC: 42.4% vs. 46.0%, p=0.50). After adjusting for age and gender presence of the PAI-1 4G/4G genotype was associated with a non-significant odds ratio of 1.21 (95% confidence interval [95% CI]: 0.77 - 1.92, p=0.41), while homozygosity for the t-PA -7351C allele yielded a non-significant odds ratio of 0.91 (95% CI: 0.62 – 1.33, p=0.62) for CSC. Conclusion: The present study indicates that increased t-PA antigen plasma concentrations are associated with a higher risk for CSC. In contrast, the present data suggest that neither ETP levels nor the - t-PA -7351C>T and the PAI-1 4G/5G gene polymorphisms are major risk factors for CSC.