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 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.

The family of the interleukin‐1 receptors

“…For IL‐1R2, the SNP rs2302589 was found to be significantly associated with ankylosing spondylitis, whereas the rs2310173 genotype GT was mildly protective only in HLA‐B7 positive patients . The minor G allele of rs2072476 was associated to reduction of risk of pre‐term birth in Indian women .…”

Association study between killer immunoglobulin‐like receptor polymorphisms and ankylosing spondylitis disease: An updated meta‐analysis

“…AS usually happens in the third decade of life and affects men more frequently than women at a ratio of 2:1 . Notwithstanding that genetics, environment and epigenetics have been implicated, the exact etiology and pathogenesis of AS and other spondyloarthropathies (SpA) still remain unknown . However, the two central characteristics that may be worthy of explanation are new osteogenesis and inflammation, particularly in the spine .…”

“…Notwithstanding that genetics, environment and epigenetics have been implicated, [5][6][7][8][9][10][11][12][13][14][15][16][17] the exact etiology and pathogenesis of AS and other spondyloarthropathies (SpA) still remain unknown. 18,19 However, the two central characteristics that may be worthy of explanation are new osteogenesis and inflammation, particularly in the spine.…”

AB0112 Interferon-regulated genes (IRG) signatures differentiate groups of as patients and are associated with ANTI-TNF response: pilot data

“…standard:0, No swelling;1, Slight redness and swelling;2, Moderate redness and swelling of ankle; 3, Severe redness and swelling of the entire paw;4, Maximally inflamed limb with involvement of multiple joints [3] ). Day 28-42, hind foot redness and swelling of the mouse continued to develop and extended to the forefoot.…”

“…However, two SAEs occurred in the extension of the study: tonsillitis (suspected to be related to study drug) and myocardial infarction (non related), both fully recovered. Secukinumab induced a rapid and highly significant improvement in SJC [2,[8][9][10][11][12][13][14][15][16]3]p=0,001), which was associated with decreased production of MMP-3, a validated biomarker of inflammation in pSpA, 1 by peripheral blood cells in the TruCulture system (see figure). With exception of a decrease in IL-17A, the TruCulture system did not reveal any impact of secukinumab on the capacity of peripheral blood cells to produce a broad panel of cytokines and chemokines upon stimulation.…”