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

Abstract

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). TheCTLA4gene 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 inCTLA4showed 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 thatCD28andICOSgenes may be associated with a risk of RA in Koreans.Clin Chem Lab Med 2010;48:345–53.

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