CIITA gene variants are associated with rheumatoid arthritis in Scandinavian populations

Genes Immun. 2012 Jul;13(5):431-6. doi: 10.1038/gene.2012.11. Epub 2012 Apr 19.


Expression of the major autoimmune risk loci DRB1 and DQB1 is regulated by the class II MHC (major histocompatibility complex) transactivator (CIITA), making the CIITA gene a strong autoimmune risk locus candidate. A CIITA promoter single-nucleotide polymorphism (SNP), rs3087456 (-168 A/G), has indeed been associated with several autoimmune diseases, including rheumatoid arthritis (RA). Recently, an intronic SNP rs8048002 has been suggested as a better susceptibility marker in Addison's disease. Therefore, we tested both SNPs in a panel of autoimmune diseases, consisting of Norwegian patients with RA (n=819), juvenile idiopathic arthritis (JIA; n=524), or type 1 diabetes (T1D; n=1211), and 2149 controls. We also included an independent Swedish RA cohort (n=2503) and controls (n=1416). Both rs3087456 and rs8048002 were significantly associated with RA (combined Norwegian and Swedish patients P(corrected)=0.012 and P(corrected)=0.0016, respectively), but not with JIA or T1D. Meta-analysis of 16 RA cohorts confirmed rs3087456 with only marginal significance (P=0.016). However, results were stronger in the Scandinavian subgroup (4 cohorts, P=3.8 × 10(-4)), indicating a population-dependent effect. A similar pattern was observed in a meta-analysis of rs8048002. Our results support involvement of CIITA in RA, but imply that this is population dependent and that the aetiological variant is yet to be discovered.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Arthritis, Rheumatoid / genetics*
  • Autoantibodies / immunology
  • Epitopes / immunology
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Meta-Analysis as Topic
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide
  • Scandinavian and Nordic Countries
  • Trans-Activators / genetics*
  • White People / genetics*


  • Autoantibodies
  • Epitopes
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Trans-Activators