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

Rheumatol Int. 2016 Mar;36(3):429-35. doi: 10.1007/s00296-015-3391-1. Epub 2015 Nov 21.

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.

Keywords: ANTXR2; Ankylosing spondylitis; CARD9; IL1R2; SNAPC4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CARD Signaling Adaptor Proteins / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • HLA-B27 Antigen / immunology
  • Heterozygote
  • Homozygote
  • Humans
  • Iran / epidemiology
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Protective Factors
  • Receptors, Interleukin-1 Type II / genetics*
  • Receptors, Peptide / genetics*
  • Risk Factors
  • Severity of Illness Index
  • Spondylitis, Ankylosing / diagnosis
  • Spondylitis, Ankylosing / ethnology
  • Spondylitis, Ankylosing / genetics*
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • ANTXR2 protein, human
  • CARD Signaling Adaptor Proteins
  • CARD9 protein, human
  • DNA-Binding Proteins
  • HLA-B27 Antigen
  • IL1R2 protein, human
  • Receptors, Interleukin-1 Type II
  • Receptors, Peptide
  • SNAPC4 protein, human
  • Transcription Factors