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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Tate, Jillian R. / Tsongalis, Gregory J.

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

Young Ock Kim1, 2 / Hak Jae Kim3 / Su Kang Kim2 / Joo-Ho Chung2 / Seung-Jae Hong2, 4

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

2Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Korea

3College of Medicine, Soonchunhyang University, Chunan, Korea

4Department of Rheumatology, Kyung Hee University, Seoul, Korea

Corresponding author: Seung-Jae Hong, Department of Rheumatology and Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemoon-Gu, Seoul 130-701, Korea Phone: +82-2-961-0281, Fax: +82-2-968-0560,

Citation Information: Clinical Chemistry and Laboratory Medicine. Volume 48, Issue 3, Pages 345–353, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2010.074, February 2010

Publication History

Published Online:


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.

Clin Chem Lab Med 2010;48:345–53.

Keywords: CD28; CTLA4; ICOS; immunoregulatory gene; polymorphism; rheumatoid arthritis

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