Rheumatology Advance Access originally published online on May 18, 2005
Rheumatology 2005 44(9):1115-1121; doi:10.1093/rheumatology/keh689
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Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile rheumatoid arthritis
Departments of Paediatrics, 1 Internal Medicine and 2 Radiology, University of Manitoba, Winnipeg, Manitoba, 3 Department of Paediatrics, University of British Columbia, Vancouver, British Columbia, 4 Department of Paediatrics, University of Saskatchewan, Saskatoon, Saskatchewan and 5 Canadian Blood Transfusion Service, Winnipeg, Manitoba, Canada.
Correspondence to: K. Oen, Arthritis Centre, Health Sciences Centre, RR149-800 Sherbrook Street, Winnipeg, Manitoba R3A 1M4, Canada. E-mail: koen{at}exchange.hsc.mb.ca.
Objectives. Single nucleotide polymorphisms (SNPs) in cytokine genes have been associated with risk of a number of autoimmune diseases. Moreover, some SNPs are associated with variations in rates of in vitro gene expression, and it is therefore possible that these functional polymorphisms may differentially affect inflammatory processes and disease outcome. This project's objective was to determine whether cytokine genotypes correlate with disease outcomes in patients with juvenile rheumatoid arthritis (JRA).
Methods. Genotypes of SNPs of pro-inflammatory cytokines, tumour necrosis factor-
–308G 
A, interleukin-6 (IL-6) –174G C and interferon-gamma +874G A, and anti-inflammatory, immunosuppressive cytokines, interleukin-10 –1082G A, –819C T and –592A C and transforming growth factor-ß1 (TGF-ß1) codon 10T C and codon 25G C, were determined for patients with JRA who previously participated in a long-term outcome study. Cytokine genotypes and clinical variables showing significant correlations with clinical outcomes at the = 0.100 level in univariate analyses were entered in multivariate tests.
Results. In multivariate tests, the IL-6 genotype –174G/G was positively correlated with pain [regression coefficient B = 0.899, 95% confidence intervals (CI) 0.185, 1.612, P = 0.014]. The homozygous TGF-ß1 codon 25G/G genotype showed a protective effect against joint space narrowing on radiographs taken within 2 yr of disease onset, but confidence intervals were wide [odds ratio (OR) 0.176, 95% CI 0.037, 0.837 P = 0.029].
Conclusions. The correlation of IL-6 genotype with pain and the possible association of the TGF-ß1 codon 25 genotype with short-term radiographic damage (G/C with greater risk and G/G with decreased risk) suggests that both these polymorphisms may be useful early prognostic indicators. Further studies of the relation between cytokine genotypes and outcomes in patients with all forms of juvenile idiopathic arthritis (JIA) are warranted.
KEY WORDS: Juvenile idiopathic arthritis, Juvenile rheumatoid arthritis, Cytokine genes, Long-term outcomes
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