Association of the CD28/CTLA4/ICOS polymorphisms with susceptibility to rheumatoid arthritis

Clin Chem Lab Med. 2010 Mar;48(3):345-53. doi: 10.1515/CCLM.2010.074.


Background: Rheumatoid arthritis (RA) is currently thought to be an immune-mediated disease where the host's genes and environmental factors interact. Some of the immuno-regulatory genes that are responsible for an individual's susceptibility to RA have been identified. The co-stimulatory receptor gene cluster on chromosome 2q33 encodes for both the positive T-cell regulators CD28 molecule (CD28) and inducible T-cell co-stimulator (ICOS), and the negative regulator cytotoxic T-lymphocyte-associated protein 4 (CTLA4). The CTLA4 gene has been implicated in several immune-mediated diseases, but it is not known whether RA is associated with any of these genes.

Methods: We conducted single nucleotide polymorphism (SNP) genotyping with direct sequencing and restriction fragment length polymorphism for 308 Korean patients with RA and 412 healthy control subjects. For the case-control analysis, SNPStats, SNPAnalyzer and Helixtree programs were used.

Results: Although none of the polymorphisms in CTLA4 showed a significant association with RA, CD28 and ICOS showed a significant association with RA [rs2140148 in CD28, p = 0.022, odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.07-2.40 in the dominant model, rs6726035 in ICOS, p = 0.032, OR = 1.28, 95% CI = 1.02-1.60 in the codominant model].

Conclusions: Our results suggest that CD28 and ICOS genes may be associated with a risk of RA in Koreans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / genetics*
  • Antigens, Differentiation, T-Lymphocyte / genetics*
  • Arthritis, Rheumatoid / genetics*
  • Asian People / genetics*
  • CD28 Antigens / genetics*
  • CTLA-4 Antigen
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Inducible T-Cell Co-Stimulator Protein
  • Male
  • Middle Aged
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Republic of Korea


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein