Association of the CD28/CTLA4/ICOS polymorphisms with susceptibility to rheumatoid arthritis.
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.
Kim
Young Ock
YO
Ginseng and Medicinal Plants Research Institute Rural Development Administration, Chungbuk, Korea.
Kim
Hak Jae
HJ
Kim
Su Kang
SK
Chung
Joo-Ho
JH
Hong
Seung-Jae
SJ
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein