Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

Anne Hinks; Xiayi Ke; Anne Barton; Steve Eyre; John Bowes; Jane Worthington; Anthony G. Wilson; Ann Morgan; Paul Emery; Sophia Steer; Lynne Hocking; David M. Reid; Paul Wordsworth; Pille Harrison; Deborah Symmons; M. Abinum; M. Becker; A. Bell; A. Craft; E. Crawley; J. David; H. Foster; J. Gardener-Medwin; J. Griffin; A. Hall; M. Hall; A. Herrick; P. Hollingworth; L. Holt; S. Jones; G. Pountain; C. Ryder; T. Southwood; I. Stewart; H. Venning; L. Wedderburn; P. Woo; S. Wyatt; Philip Conaghan; Mark Quinn; Anne Maree Keenan; Elizabeth Hensor; Julie Kitcheman; Andrew Gough; Michael Green; Richard Reece; Lesley Hordon; Philip Helliwell; Richard Melsom; Sheelagh Doherty; Ade Adebajo; Andrew Harvey; Steve Jarrett; Gareth Huson; Amanda Isdale; Mike Martin; Zinaid Karim; Dennis McGonagle; Colin Pease; Sally Cox; Victoria Bejarano; Jackie Nam; Claire Brown; Christine Thomas; David Pickles; Alison Hammond; Beverley Neville; Alan Fairclough; Caroline Nunns; Anne Gill; Julie Green; Belinda Rhys-Evans; Barbara Padwell; Julie Madden; Lynda Taylor; Sally Smith; Heather King; Jill Firth; Jayne Heard; Linda Sigsworth; Diane Corscadden; Karen Henshaw; Lubna Haroon Rashid; Stephen G. Martin; James I. Robinson; Susan D. Thompson; Carl D. Langefeld; David N. Glass; Wendy Thomson

doi:10.1002/art.24187

Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

Anne Hinks, Xiayi Ke, Anne Barton, Steve Eyre, John Bowes, Jane Worthington, Anthony G. Wilson, Ann Morgan, Paul Emery, Sophia Steer, Lynne Hocking, David M. Reid, Paul Wordsworth, Pille Harrison, Deborah Symmons, M. Abinum, M. Becker, A. Bell, A. Craft, E. CrawleyJ. David, H. Foster, J. Gardener-Medwin, J. Griffin, A. Hall, M. Hall, A. Herrick, P. Hollingworth, L. Holt, S. Jones, G. Pountain, C. Ryder, T. Southwood, I. Stewart, H. Venning, L. Wedderburn, P. Woo, S. Wyatt, Philip Conaghan, Mark Quinn, Anne Maree Keenan, Elizabeth Hensor, Julie Kitcheman, Andrew Gough, Michael Green, Richard Reece, Lesley Hordon, Philip Helliwell, Richard Melsom, Sheelagh Doherty, Ade Adebajo, Andrew Harvey, Steve Jarrett, Gareth Huson, Amanda Isdale, Mike Martin, Zinaid Karim, Dennis McGonagle, Colin Pease, Sally Cox, Victoria Bejarano, Jackie Nam, Claire Brown, Christine Thomas, David Pickles, Alison Hammond, Beverley Neville, Alan Fairclough, Caroline Nunns, Anne Gill, Julie Green, Belinda Rhys-Evans, Barbara Padwell, Julie Madden, Lynda Taylor, Sally Smith, Heather King, Jill Firth, Jayne Heard, Linda Sigsworth, Diane Corscadden, Karen Henshaw, Lubna Haroon Rashid, Stephen G. Martin, James I. Robinson, Susan D. Thompson, Carl D. Langefeld, David N. Glass, Wendy Thomson

Research output: Contribution to journal › Article › peer-review

Abstract

Objective. IL2RA/CD25, the gene for interleukin-2 receptor α, 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 = 4.9 × 10-5). 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. © 2009, American College of Rheumatology.

Original language	English
Pages (from-to)	251-257
Number of pages	6
Journal	Arthritis Care & Research
Volume	60
Issue number	1
DOIs	https://doi.org/10.1002/art.24187
Publication status	Published - Jan 2009

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Hinks, A., Ke, X., Barton, A., Eyre, S., Bowes, J., Worthington, J., Wilson, A. G., Morgan, A., Emery, P., Steer, S., Hocking, L., Reid, D. M., Wordsworth, P., Harrison, P., Symmons, D., Abinum, M., Becker, M., Bell, A., Craft, A., ... Thomson, W. (2009). Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis Care & Research, 60(1), 251-257. https://doi.org/10.1002/art.24187

@article{add092ba1892417b80b3ab9ef071d207,

title = "Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis",

abstract = "Objective. IL2RA/CD25, the gene for interleukin-2 receptor α, 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 = 4.9 × 10-5). 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. {\textcopyright} 2009, American College of Rheumatology.",

author = "Anne Hinks and Xiayi Ke and Anne Barton and Steve Eyre and John Bowes and Jane Worthington and Wilson, {Anthony G.} and Ann Morgan and Paul Emery and Sophia Steer and Lynne Hocking and Reid, {David M.} and Paul Wordsworth and Pille Harrison and Deborah Symmons and M. Abinum and M. Becker and A. Bell and A. Craft and E. Crawley and J. David and H. Foster and J. Gardener-Medwin and J. Griffin and A. Hall and M. Hall and A. Herrick and P. Hollingworth and L. Holt and S. Jones and G. Pountain and C. Ryder and T. Southwood and I. Stewart and H. Venning and L. Wedderburn and P. Woo and S. Wyatt and Philip Conaghan and Mark Quinn and Keenan, {Anne Maree} and Elizabeth Hensor and Julie Kitcheman and Andrew Gough and Michael Green and Richard Reece and Lesley Hordon and Philip Helliwell and Richard Melsom and Sheelagh Doherty and Ade Adebajo and Andrew Harvey and Steve Jarrett and Gareth Huson and Amanda Isdale and Mike Martin and Zinaid Karim and Dennis McGonagle and Colin Pease and Sally Cox and Victoria Bejarano and Jackie Nam and Claire Brown and Christine Thomas and David Pickles and Alison Hammond and Beverley Neville and Alan Fairclough and Caroline Nunns and Anne Gill and Julie Green and Belinda Rhys-Evans and Barbara Padwell and Julie Madden and Lynda Taylor and Sally Smith and Heather King and Jill Firth and Jayne Heard and Linda Sigsworth and Diane Corscadden and Karen Henshaw and Rashid, {Lubna Haroon} and Martin, {Stephen G.} and Robinson, {James I.} and Thompson, {Susan D.} and Langefeld, {Carl D.} and Glass, {David N.} and Wendy Thomson",

year = "2009",

month = jan,

doi = "10.1002/art.24187",

language = "English",

volume = "60",

pages = "251--257",

journal = "Arthritis Care & Research",

issn = "2151-464X",

publisher = "John Wiley & Sons Ltd",

number = "1",

}

Hinks, A, Ke, X, Barton, A , Eyre, S , Bowes, J , Worthington, J, Wilson, AG, Morgan, A, Emery, P, Steer, S, Hocking, L, Reid, DM, Wordsworth, P, Harrison, P, Symmons, D, Abinum, M, Becker, M, Bell, A, Craft, A, Crawley, E, David, J, Foster, H, Gardener-Medwin, J, Griffin, J, Hall, A, Hall, M, Herrick, A, Hollingworth, P, Holt, L, Jones, S, Pountain, G, Ryder, C, Southwood, T, Stewart, I, Venning, H, Wedderburn, L, Woo, P, Wyatt, S, Conaghan, P, Quinn, M, Keenan, AM, Hensor, E, Kitcheman, J, Gough, A, Green, M, Reece, R, Hordon, L, Helliwell, P, Melsom, R, Doherty, S, Adebajo, A, Harvey, A, Jarrett, S, Huson, G, Isdale, A, Martin, M, Karim, Z, McGonagle, D, Pease, C, Cox, S, Bejarano, V, Nam, J, Brown, C, Thomas, C, Pickles, D, Hammond, A, Neville, B, Fairclough, A, Nunns, C, Gill, A, Green, J, Rhys-Evans, B, Padwell, B, Madden, J, Taylor, L, Smith, S, King, H, Firth, J, Heard, J, Sigsworth, L, Corscadden, D, Henshaw, K, Rashid, LH, Martin, SG, Robinson, JI, Thompson, SD, Langefeld, CD, Glass, DN & Thomson, W 2009, 'Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis', Arthritis Care & Research, vol. 60, no. 1, pp. 251-257. https://doi.org/10.1002/art.24187

TY - JOUR

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 - Wilson, Anthony G.

AU - Morgan, Ann

AU - Emery, Paul

AU - Steer, Sophia

AU - Hocking, Lynne

AU - Reid, David M.

AU - Wordsworth, Paul

AU - Harrison, Pille

AU - Symmons, Deborah

AU - Abinum, M.

AU - Becker, M.

AU - Bell, A.

AU - Craft, A.

AU - Crawley, E.

AU - David, J.

AU - Foster, H.

AU - Gardener-Medwin, J.

AU - Griffin, J.

AU - Hall, A.

AU - Hall, M.

AU - Herrick, A.

AU - Hollingworth, P.

AU - Holt, L.

AU - Jones, S.

AU - Pountain, G.

AU - Ryder, C.

AU - Southwood, T.

AU - Stewart, I.

AU - Venning, H.

AU - Wedderburn, L.

AU - Woo, P.

AU - Wyatt, S.

AU - Conaghan, Philip

AU - Quinn, Mark

AU - Keenan, Anne Maree

AU - Hensor, Elizabeth

AU - Kitcheman, Julie

AU - Gough, Andrew

AU - Green, Michael

AU - Reece, Richard

AU - Hordon, Lesley

AU - Helliwell, Philip

AU - Melsom, Richard

AU - Doherty, Sheelagh

AU - Adebajo, Ade

AU - Harvey, Andrew

AU - Jarrett, Steve

AU - Huson, Gareth

AU - Isdale, Amanda

AU - Martin, Mike

AU - Karim, Zinaid

AU - McGonagle, Dennis

AU - Pease, Colin

AU - Cox, Sally

AU - Bejarano, Victoria

AU - Nam, Jackie

AU - Brown, Claire

AU - Thomas, Christine

AU - Pickles, David

AU - Hammond, Alison

AU - Neville, Beverley

AU - Fairclough, Alan

AU - Nunns, Caroline

AU - Gill, Anne

AU - Green, Julie

AU - Rhys-Evans, Belinda

AU - Padwell, Barbara

AU - Madden, Julie

AU - Taylor, Lynda

AU - Smith, Sally

AU - King, Heather

AU - Firth, Jill

AU - Heard, Jayne

AU - Sigsworth, Linda

AU - Corscadden, Diane

AU - Henshaw, Karen

AU - Rashid, Lubna Haroon

AU - Martin, Stephen G.

AU - Robinson, James I.

AU - Thompson, Susan D.

AU - Langefeld, Carl D.

AU - Glass, David N.

AU - Thomson, Wendy

PY - 2009/1

Y1 - 2009/1

N2 - Objective. IL2RA/CD25, the gene for interleukin-2 receptor α, 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 = 4.9 × 10-5). 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. © 2009, American College of Rheumatology.

AB - Objective. IL2RA/CD25, the gene for interleukin-2 receptor α, 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 = 4.9 × 10-5). 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. © 2009, American College of Rheumatology.

U2 - 10.1002/art.24187

DO - 10.1002/art.24187

M3 - Article

SN - 2151-464X

VL - 60

SP - 251

EP - 257

JO - Arthritis Care & Research

JF - Arthritis Care & Research

IS - 1

ER -

Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

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