Berthold Hoppe1,2, Christian Schwedler2, Hildrun Haibel3, Maryna Verba3, Fabian Proft3, Mikhail Protopopov3, Hans-Gert Heuft4, Valeria Rios Rodriguez3, Anke Edelmann5, Martin Rudwaleit3,6, Joachim Sieper3, Denis Poddubnyy3,7. 1. Institute of Laboratory Medicine, Unfallkrankenhaus Berlin, 12683 Berlin, Germany. 2. Institute 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, Germany. 3. Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, 12200 Berlin, Germany. 4. Institute of Transfusion Medicine, Otto-von-Guericke Universität Magdeburg, 39120 Magdeburg, Germany. 5. Department of Molecular Diagnostics, Labor Berlin-Charité Vivantes GmbH, 13353 Berlin, Germany. 6. Department of Internal Medicine and Rheumatology, Klinikum Bielefeld Rosenhöhe, 33647 Bielefeld, Germany. 7. Department of Epidemiology, German Rheumatism Research Centre, 10117 Berlin, Germany.
Abstract
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) α2-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; p < 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) (p < 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.
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) α2-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; p < 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) (p < 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.
Authors: J P Collet; D Park; C Lesty; J Soria; C Soria; G Montalescot; J W Weisel Journal: Arterioscler Thromb Vasc Biol Date: 2000-05 Impact factor: 8.311
Authors: A Tybjaerg-Hansen; B Agerholm-Larsen; S E Humphries; S Abildgaard; P Schnohr; B G Nordestgaard Journal: J Clin Invest Date: 1997-06-15 Impact factor: 14.808
Authors: Maxime Dougados; Paternotte Simon; Juergen Braun; Ruben Burgos-Vargas; Walter P Maksymowych; Joachim Sieper; Désirée van der Heijde Journal: Ann Rheum Dis Date: 2010-09-09 Impact factor: 19.103
Authors: M C W Creemers; M J A M Franssen; M A van't Hof; F W J Gribnau; L B A van de Putte; P L C M van Riel Journal: Ann Rheum Dis Date: 2004-03-29 Impact factor: 19.103