Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis
Objective: Coagulation and fibrinolysis are interrelated with the expression of vascular endothelial growth factor (VEGF), which frequently is increased in axial spondyloarthritis (axSpA). We tested whether (i) α<sub>2</sub>-antiplasmin (A2AP) Arg6Trp, (ii) fibrinogen, factor XIII A-subu...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9383 |
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| author | Berthold Hoppe Christian Schwedler Hildrun Haibel Maryna Verba Fabian Proft Mikhail Protopopov Hans-Gert Heuft Valeria Rios Rodriguez Anke Edelmann Martin Rudwaleit Joachim Sieper Denis Poddubnyy |
| author_facet | Berthold Hoppe Christian Schwedler Hildrun Haibel Maryna Verba Fabian Proft Mikhail Protopopov Hans-Gert Heuft Valeria Rios Rodriguez Anke Edelmann Martin Rudwaleit Joachim Sieper Denis Poddubnyy |
| author_sort | Berthold Hoppe |
| collection | DOAJ |
| description | Objective: Coagulation and fibrinolysis are interrelated with the expression of vascular endothelial growth factor (VEGF), which frequently is increased in axial spondyloarthritis (axSpA). We tested whether (i) α<sub>2</sub>-antiplasmin (A2AP) Arg6Trp, (ii) fibrinogen, factor XIII A-subunit or B-subunit genotypes are associated with VEGF levels and assessed whether the known association between elevated VEGF and radiographic spinal progression in axSpA depends on genetic background. Methods: One hundred and eighty-six axSpA patients from the German Spondyloarthritis Inception Cohort were genotyped, characterized for VEGF levels, and statistically analyzed. The association between VEGF and radiographic spinal progression was assessed in dependence on genetic background in stratified analyses. Results: A2AP 6Trp carriage was associated with VEGF elevation (OR: 2.37, 95% CI: 1.06–5.29) and VEGF levels (6Trp, 455 ± 334 pg/mL; 6Arg/Arg, 373 ± 293 pg/mL; <i>p</i> < 0.008). Association between elevated VEGF and radiographic spinal progression in axSpA (OR: 3.11, 95% CI: 1.02–8.82) depended remarkably on the fibrinogen (FGA) genotype. When considering axSpA patients with elevated VEGF, in FGA rs6050A>G wild types, 42.1% of patients (8 of 19) progressed, while in G-allele carriers, no radiographic progression happened (0 of 13) (<i>p</i> < 0.04). Conclusions: The A2AP Arg6Trp genotype seems to influence VEGF levels in axSpA. The predictive value of VEGF elevations in respect of radiographic spinal progression in axSpA depends on FGA genotypes. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:12:29Z |
| publishDate | 2020-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3d75b9d852be4d44a38afb1cfa5eda4a2023-11-21T00:03:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124938310.3390/ijms21249383Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial SpondyloarthritisBerthold Hoppe0Christian Schwedler1Hildrun Haibel2Maryna Verba3Fabian Proft4Mikhail Protopopov5Hans-Gert Heuft6Valeria Rios Rodriguez7Anke Edelmann8Martin Rudwaleit9Joachim Sieper10Denis Poddubnyy11Institute of Laboratory Medicine, Unfallkrankenhaus Berlin, 12683 Berlin, GermanyInstitute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyInstitute of Transfusion Medicine, Otto-von-Guericke Universität Magdeburg, 39120 Magdeburg, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyDepartment of Molecular Diagnostics, Labor Berlin–Charité Vivantes GmbH, 13353 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyDepartment of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, GermanyObjective: Coagulation and fibrinolysis are interrelated with the expression of vascular endothelial growth factor (VEGF), which frequently is increased in axial spondyloarthritis (axSpA). We tested whether (i) α<sub>2</sub>-antiplasmin (A2AP) Arg6Trp, (ii) fibrinogen, factor XIII A-subunit or B-subunit genotypes are associated with VEGF levels and assessed whether the known association between elevated VEGF and radiographic spinal progression in axSpA depends on genetic background. Methods: One hundred and eighty-six axSpA patients from the German Spondyloarthritis Inception Cohort were genotyped, characterized for VEGF levels, and statistically analyzed. The association between VEGF and radiographic spinal progression was assessed in dependence on genetic background in stratified analyses. Results: A2AP 6Trp carriage was associated with VEGF elevation (OR: 2.37, 95% CI: 1.06–5.29) and VEGF levels (6Trp, 455 ± 334 pg/mL; 6Arg/Arg, 373 ± 293 pg/mL; <i>p</i> < 0.008). Association between elevated VEGF and radiographic spinal progression in axSpA (OR: 3.11, 95% CI: 1.02–8.82) depended remarkably on the fibrinogen (FGA) genotype. When considering axSpA patients with elevated VEGF, in FGA rs6050A>G wild types, 42.1% of patients (8 of 19) progressed, while in G-allele carriers, no radiographic progression happened (0 of 13) (<i>p</i> < 0.04). Conclusions: The A2AP Arg6Trp genotype seems to influence VEGF levels in axSpA. The predictive value of VEGF elevations in respect of radiographic spinal progression in axSpA depends on FGA genotypes.https://www.mdpi.com/1422-0067/21/24/9383fibrinolysisα<sub>2</sub>-antiplasminfibrinogenfactor XIIIspondyloarthritisvascular endothelial growth factor |
| spellingShingle | Berthold Hoppe Christian Schwedler Hildrun Haibel Maryna Verba Fabian Proft Mikhail Protopopov Hans-Gert Heuft Valeria Rios Rodriguez Anke Edelmann Martin Rudwaleit Joachim Sieper Denis Poddubnyy Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis International Journal of Molecular Sciences fibrinolysis α<sub>2</sub>-antiplasmin fibrinogen factor XIII spondyloarthritis vascular endothelial growth factor |
| title | Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis |
| title_full | Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis |
| title_fullStr | Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis |
| title_full_unstemmed | Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis |
| title_short | Relation of α<sub>2</sub>-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis |
| title_sort | relation of α sub 2 sub antiplasmin genotype and genetic determinants of fibrinogen synthesis and fibrin clot formation with vascular endothelial growth factor level in axial spondyloarthritis |
| topic | fibrinolysis α<sub>2</sub>-antiplasmin fibrinogen factor XIII spondyloarthritis vascular endothelial growth factor |
| url | https://www.mdpi.com/1422-0067/21/24/9383 |
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