Determination of Il1 R2, Antxr2, Card9, and Snapc4 Single Nucleotide Polymorphisms in Iranian Patients With Ankylosing Spondylitis Publisher Pubmed



Momenzadeh P^{1, 2} ; Mahmoudi M^{2, 6} ; Beigy M^{2, 3} ; Garshasbi M⁴ ; Vodjdanian M² ; Farazmand A^{1, 5, 7} ; Jamshidi AR² Show Affiliations
Source: Rheumatology International Published:2016

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 HLA-B27 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. © 2015, Springer-Verlag Berlin Heidelberg.