Determination of IL1 R2, ANTXR2, CARD9, and SNAPC4 single nucleotide polymorphisms in Iranian patients with ankylosing spondylitis


Abstract: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin, while both genetic and environmental factors have been demonstrated to be etiologically involved. Recent genome-wide association and replication studies have suggested that anthrax toxin receptor 2 (ANTXR2), interleukin-1 receptor 2 (IL1R2), caspase recruitment domain-containing protein 9 (CARD9), and small nuclear RNA-activating complex polypeptide 4 (SNAPC4) seem to be associated with AS pathogenesis. This case–control study was performed on 349 unrelated AS patients and 469 age- and gender-matched healthy controls, to investigate whether these non-MHC genes (IL1R2 rs2310173, ANTXR2 rs4333130, CARD9 rs4077515, and SNAPC4 rs3812571) influence the AS risk in Iranian population. ANTXR2 rs4333130 allele C (p = 0.0328; OR 0.744, 95 % CI 0.598–0.927) and genotype CC (p = 0.0108; OR 0.273, 95 % CI 0.123–0.605) were found to be significantly protective against AS. No other associations were found between AS and studied genes. The association between ANTXR2 rs4333130 and AS was independent of HLAB27 status. Moreover, we found clinical disease severity scores (BASDAI and BASFI) and pain score were higher in ANTXR2 rs4333130 CT genotype. However, we observed that CARD9 allele C (p = 0.012) and genotype CC (p = 0.012) were significant protective factors against AS only in HLA-B27-negative patients, and IL1R2 rs2310173 genotype GT was mildly protective against AS only in HLA-B27-negative status. These findings support the role of non-MHC pathogenic pathways in susceptibility to AS and warrants more comprehensive studies focusing on these non-MHC pathways for developing novel therapeutic strategies. Keywords Ankylosing spondylitis · IL1R2 · ANTXR2 · CARD9 · SNAPC4