Relation of a2-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

卷:21

Mikhail Protopopov¹  Hildrun Haibel¹  Maryna Verba¹  Fabian Proft¹  Martin Rudwaleit¹  Denis Poddubnyy¹  Joachim Sieper¹  Valeria Rios Rodriguez¹  Anke Edelmann²  Christian Schwedler³  Berthold Hoppe⁴  Hans-Gert Heuft⁵ 

[1] Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité–Universitätsmedizin Berlin, 12200 Berlin, Germany;

[2] Department of Molecular Diagnostics, Labor Berlin–Charité Vivantes GmbH, 13353 Berlin, Germany;

[3] 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;

[4] Institute of Laboratory Medicine, Unfallkrankenhaus Berlin, 12683 Berlin, Germany;

[5] Institute of Transfusion Medicine, Otto-von-Guericke Universität Magdeburg, 39120 Magdeburg, Germany;

关键词: fibrinolysis;    a₂-antiplasmin;    fibrinogen;    factor XIII;    spondyloarthritis;    vascular endothelial growth factor;   

DOI  :  10.3390/ijms21249383

来源: DOAJ

【 摘 要 】

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) a₂-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.

【 授权许可】

Unknown