Cytokine genotypes correlate with pain and radiologically defined joint damage in patients with juvenile rheumatoid arthritis.
OBJECTIVE
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-alpha -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-beta1 (TGF-beta1) 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 alpha = 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-beta1 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-beta1 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.
Oen
K
K
Department of Paediatrics, University of Manitoba, Winnipeg, Canada. koen@exchange.hsc.mb.ca
Malleson
P N
PN
Cabral
D A
DA
Rosenberg
A M
AM
Petty
R E
RE
Nickerson
P
P
Reed
M
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001171:Arthritis, Juvenile / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D002648:Child; D016207:Cytokines / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D015999:Multivariate Analysis; D010146:Pain / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011859:Radiography; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D015850:Interleukin-6; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1