Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis.
OBJECTIVE
IL2RA/CD25, the gene for interleukin-2 receptor alpha, is emerging as a general susceptibility gene for autoimmune diseases because of its role in the development and function of regulatory T cells and the association of single-nucleotide polymorphisms (SNPs) within this gene with type 1 diabetes mellitus (DM), Graves' disease, rheumatoid arthritis (RA), and multiple sclerosis (MS). The aim of this study was to determine whether SNPs within the IL2RA/CD25 gene are associated with juvenile idiopathic arthritis (JIA).


METHODS
Three SNPs within the IL2RA/CD25 gene, that previously showed evidence of an association with either RA, MS, or type 1 DM, were selected for genotyping in UK JIA cases (n=654) and controls (n=3,849). Data for 1 SNP (rs2104286) were also available from North American JIA cases (n=747) and controls (n=1,161). Association analyses were performed using Plink software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.


RESULTS
SNP rs2104286 within the IL2RA/CD25 gene was significantly associated with UK JIA cases (OR for the allele 0.76 [95% CI 0.66-0.88], P for trend=0.0002). A second SNP (rs41295061) also showed modest evidence for association with JIA (OR 0.80 [95% CI 0.63-1.0], P=0.05). Association with rs2104286 was convincingly replicated in the North American JIA cohort (OR 0.84 [95% CI 0.65-0.99], P for trend=0.05). Meta-analysis of the 2 cohorts yielded highly significant evidence of association with JIA (OR 0.76 [95% CI 0.62-0.88], P=4.9x10(-5)).


CONCLUSIONS
These results provide strong evidence that the IL2RA/CD25 gene represents a JIA susceptibility locus. Further investigation of the gene using both genetic and functional approaches is now required.
Hinks
Anne
A
University of Manchester, Manchester, UK. Anne.Hinks@manchester.ac.uk
Ke
Xiayi
X
Barton
Anne
A
Eyre
Steve
S
Bowes
John
J
Worthington
Jane
J
Thompson
Susan D
SD
Langefeld
Carl D
CD
Glass
David N
DN
Thomson
Wendy
W
D001171:Arthritis, Juvenile / Q000235:genetics*; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D009656:North America; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D006113:United Kingdom
C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit