Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

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Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

http://www3.interscience.wiley.com/journal/121589870/abstract

Abstract

Objective

IL2RA/CD25, the gene for interleukin-2 receptor , 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. A second SNP (rs41295061) also showed modest evidence for

association with JIA. Association with rs2104286 was convincingly replicated

in the North American JIA cohort. Meta-analysis of the 2 cohorts yielded

highly significant evidence of association with JIA.

Conclusion

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.

Anne Hinks 1 *, Xiayi Ke 1, Anne Barton 1, Steve Eyre 1, Bowes 1, Jane

Worthington 1, UK Rheumatoid Arthritis Genetics Consortium, British Society

of Paediatric and Adolescent Rheumatology Study Group, D. 2,

Carl D. Langefeld 3, N. Glass 2, Thomson 1

1University of Manchester, Manchester, UK

2Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

3Wake Forest University School of Medicine, Winston-Salem, North Carolina

email: Anne Hinks (Anne.Hinks@...)

*Correspondence to Anne Hinks, ARC Epidemiology Unit, University of

Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK