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

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

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  • 1Ginseng and Medicinal Plants Research Institute Rural Development Administration, Chungbuk, Korea.

Abstract

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.

PMID:
20113255
[PubMed - indexed for MEDLINE]
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