Relation of α2-Antiplasmin Genotype and Genetic Determinants of Fibrinogen Synthesis and Fibrin Clot Formation with Vascular Endothelial Growth Factor Level in Axial Spondyloarthritis.

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.

• Authors: 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
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 24 (Dec 09 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33317138 (Publication Type: Journal Article)

Chemical References

• Vascular Endothelial Growth Factor A
• alpha-2-Antiplasmin
• Factor VIII
• Fibrinogen

Topics

• Adult
• Factor VIII (genetics)
• Female
• Fibrinogen (genetics)
• Genotype
• Humans
• Male
• Middle Aged
• Spondylitis, Ankylosing (diagnostic imaging, genetics, metabolism)
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• alpha-2-Antiplasmin (genetics)