Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

UK Rheumatoid Arthritis Genetics Consortium, British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group

Research output: Contribution to journalArticle

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Abstract

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)). 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.
Original languageEnglish
Pages (from-to)251-257
Number of pages7
JournalArthritis & Rheumatism
Volume60
Issue number1
Early online date30 Dec 2008
DOIs
Publication statusPublished - Jan 2009

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Juvenile Arthritis
Single Nucleotide Polymorphism
Odds Ratio
Genes
Confidence Intervals
Type 1 Diabetes Mellitus
Multiple Sclerosis
Rheumatoid Arthritis
Interleukin-2 Receptor alpha Subunit
Graves Disease
Regulatory T-Lymphocytes
Autoimmune Diseases
Meta-Analysis
Software
Alleles

Keywords

  • arthritis, juvenile rheumatoid
  • cohort studies
  • gene frequency
  • genetic predisposition to disease
  • genotype
  • Great Britain
  • humans
  • interleukin-2 receptor alpha subunit
  • North America
  • polymorphism, single nucleotide
  • registries

Cite this

UK Rheumatoid Arthritis Genetics Consortium, & British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group (2009). Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis & Rheumatism, 60(1), 251-257. https://doi.org/10.1002/art.24187

Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. / UK Rheumatoid Arthritis Genetics Consortium; British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group.

In: Arthritis & Rheumatism, Vol. 60, No. 1, 01.2009, p. 251-257.

Research output: Contribution to journalArticle

UK Rheumatoid Arthritis Genetics Consortium & British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group 2009, 'Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis', Arthritis & Rheumatism, vol. 60, no. 1, pp. 251-257. https://doi.org/10.1002/art.24187
UK Rheumatoid Arthritis Genetics Consortium, British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group. Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis & Rheumatism. 2009 Jan;60(1):251-257. https://doi.org/10.1002/art.24187
UK Rheumatoid Arthritis Genetics Consortium ; British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group. / Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. In: Arthritis & Rheumatism. 2009 ; Vol. 60, No. 1. pp. 251-257.
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title = "Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis",
abstract = "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)). 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.",
keywords = "arthritis, juvenile rheumatoid, cohort studies, gene frequency, genetic predisposition to disease, genotype, Great Britain, humans, interleukin-2 receptor alpha subunit, North America, polymorphism, single nucleotide, registries",
author = "Anne Hinks and Xiayi Ke and Anne Barton and Steve Eyre and John Bowes and Jane Worthington and Thompson, {Susan D} and Langefeld, {Carl D} and Glass, {David N} and Wendy Thomson and Hocking, {Lynne J} and Reid, {David M} and {UK Rheumatoid Arthritis Genetics Consortium} and {British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group}",
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T1 - Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

AU - Hinks, Anne

AU - Ke, Xiayi

AU - Barton, Anne

AU - Eyre, Steve

AU - Bowes, John

AU - Worthington, Jane

AU - Thompson, Susan D

AU - Langefeld, Carl D

AU - Glass, David N

AU - Thomson, Wendy

AU - Hocking, Lynne J

AU - Reid, David M

AU - UK Rheumatoid Arthritis Genetics Consortium

AU - British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group

PY - 2009/1

Y1 - 2009/1

N2 - 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)). 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.

AB - 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)). 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.

KW - arthritis, juvenile rheumatoid

KW - cohort studies

KW - gene frequency

KW - genetic predisposition to disease

KW - genotype

KW - Great Britain

KW - humans

KW - interleukin-2 receptor alpha subunit

KW - North America

KW - polymorphism, single nucleotide

KW - registries

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DO - 10.1002/art.24187

M3 - Article

C2 - 19116909

VL - 60

SP - 251

EP - 257

JO - Arthritis & Rheumatism

JF - Arthritis & Rheumatism

SN - 0004-3591

IS - 1

ER -