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Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis

By A. Hinks, S. Eyre, X. Ke, A. Barton, P. Martin, E. Flynn, J. Packham, J. Worthington, W. Thomson, J. [CAPS and BSPAR study groups] Gardner-Medwin, Childhood Arthritis Prospective Study (CAPS), UKRAG Consortium and British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group

Abstract

Recent genetic studies have led to identification of numerous loci that are associated with susceptibility to autoimmune diseases. The strategy of using information from these studies has facilitated the identification of novel juvenile idiopathic arthritis (JIA) susceptibility loci, specifically, PTPN22 and IL2RA. Several novel autoimmune susceptibility loci have recently been identified, and we hypothesise that single-nucleotide polymorphisms (SNPs) within these genes may also be JIA susceptibility loci. Five SNPs within the genes AFF3, IL2/IL21, IL7R, CTLA4 and CD226, previously associated with multiple autoimmune diseases were genotyped, in a large data set of Caucasian JIA patients and controls, and tested for association with JIA. We identified two susceptibility loci for JIA, AFF3 and the IL2/IL21 region and additional weak evidence supporting an association with the CTLA4 and IL7R genes, which warrant further investigation. All results require validation in independent JIA data sets. Further characterisation of the specific causal variants will be required before functional studies can be performed

Topics: R1, QH426
Publisher: Macmillan Publishers Limited
Year: 2010
OAI identifier: oai:eprints.gla.ac.uk:48916
Provided by: Enlighten

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Citations

  1. (2008). Association between duration of symptoms and severity of disease at first presentation to paediatric rheumatology: results from the childhood arthritis prospective study. Rheumatology (Oxford) doi
  2. (2009). Association of the autoimmunity locus 4q27 with juvenile idiopathic arthritis. Arthritis Rheum doi
  3. (2009). Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis Rheum doi
  4. (2007). Association of the interleukin-2 receptor alpha (IL-2Ralpha)/CD25 gene region with Graves’ disease using a multilocus test and tag SNPs. Clin Endocrinol (Oxf) doi
  5. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. doi
  6. (2008). Autoimmune diseases: insights from genome-wide association studies. Hum Mol Genet doi
  7. (2005). Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet doi
  8. (2008). CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun doi
  9. (2009). Detecting shared pathogenesis from the shared genetics of immunerelated diseases. Nat Rev Genet doi
  10. (1996). Genetic analysis of autoimmune disease. doi
  11. (2008). Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet
  12. (2009). Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes. Hum Mol Genet doi
  13. (2009). IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet doi
  14. (2009). IL2RA/CD25 gene polymorphisms: uneven association with multiple sclerosis (MS) and type 1 diabetes (T1D). PLoS ONE doi
  15. (2001). International league of associations for rheumatology classification of juvenile idiopathic arthritis: second revision,
  16. (2007). Juvenile idiopathic arthritis. Lancet doi
  17. (2008). Lack of association of functional CTLA4 polymorphisms with juvenile idiopathic arthritis. Arthritis Rheum doi
  18. (1996). LAF-4 encodes a lymphoid nuclear protein with transactivation potential that is homologous to AF-4, the gene fused to MLL in t(4;11) leukemias. Blood
  19. (2007). Large-scale genetic fine mapping and genotypephenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet doi
  20. (2002). Long-term follow-up of 246 adults with juvenile idiopathic arthritis: functional outcome. Rheumatology doi
  21. (2007). PLINK: a tool set for whole-genome association and population-based linkage analyses. doi
  22. (2004). Replication of an association between the lymphoid tyrosine phosphatase locus (LYP/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes doi
  23. (2007). Rheumatoid arthritis association at 6q23. Nat Genet doi
  24. (2009). submitted. Association of the AFF3 gene and IL2/IL21 gene region with JIA A Hinks et al Genes and Immunityand functional association with multiple sclerosis.
  25. (2006). The association of PTPN22 with rheumatoid arthritis and juvenile idiopathic arthritis. Rheumatology (Oxford) doi
  26. (2006). The CTLA4+49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland. Exp Mol Pathol doi
  27. (2007). The Wellcome Trust Case Control Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature
  28. This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Licence. To view a copy of this licence,
  29. Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. doi

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