Background and Objectives Semaphorins are a large family of secreted and membrane bound proteins linked to their receptors in a variety of cells and implicated with the development and function of many systems (nevrous, immune, vascular) and organs (bone, heart, lung, kidney). Plexins and neuropilins are the primary semaphorin receptors. The present study addresses Plexin-A2 (PLXNA2) Rs6656560 variant in rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) susceptibility.

Materials and Methods One hundred thirty-six RA, 49 AS, 29 PsA patients and 147 controls were enrolled in the study. Polymerase chain reaction coupled with restriction fragment length polymorphism analysis was used in Rs6656560 genotyping.

Results Statistical significant difference was observed in Rs6656560 genotypes’ distribution between AS patients and controls (P = 0.041), but not between RA or PsA patients and controls (P = 0.183, P = 0.729; respectively). Similarly, significant difference was observed in Rs6656560 alleles’ distribution between AS patients and controls (P = 0.013). Since AS and PsA both belong to spondyloarthropathies (SpAs), no statistical difference was observed in genotypes’ distribution between these two groups (P = 0.178), while the statistical difference was significant between AS and RA patients (P = 0.035).

Conclusions The positive association of PLXNA2 polymorphism with AS susceptibility seems to indicate its effect in cellular semaphorin signalling related to bone development and remodelling, both of which are implicated in AS features. Additional studies are needed to ensure the revealed genetic association with AS predisposition and the effect of this variant in semaphorin/plexin complex function in specific cell types.