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Clinical Chemistry and Laboratory Medicine (CCLM)

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Volume 48, Issue 3 (Mar 2010)


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

Young Ock Kim
  • Ginseng and Medicinal Plants Research Institute Rural Development Administration, Chungbuk, Korea
  • Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Korea
/ Hak Jae Kim
  • College of Medicine, Soonchunhyang University, Chunan, Korea
/ Su Kang Kim
  • Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Korea
/ Joo-Ho Chung
  • Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Korea
/ Seung-Jae Hong
  • Kohwang Medical Research Institute, School of Medicine, Kyung Hee University, Seoul, Korea
  • Department of Rheumatology, Kyung Hee University, Seoul, Korea
Published Online: 2010-02-01 | DOI: https://doi.org/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.

Clin Chem Lab Med 2010;48:345–53.

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

About the article

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,

Received: 2009-08-07

Accepted: 2009-11-05

Published Online: 2010-02-01

Published in Print: 2010-03-01

Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2010.074.

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©2010 by Walter de Gruyter Berlin New York. Copyright Clearance Center

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