Association of the IL-10 Gene Family Locus on Chromosome 1 with Juvenile Idiopathic Arthritis (JIA) (Articolo in rivista)

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  • Association of the IL-10 Gene Family Locus on Chromosome 1 with Juvenile Idiopathic Arthritis (JIA) (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1371/journal.pone.0047673 (literal)
Alternative label
  • Ebun Omoyinmi, Paola Forabosco,Raja Hamaoui, Annette Bryant, Anne Hinks, Simona Ursu, Childhood Arthritis Prospective Study (CAPS), BSPAR study group,Childhood Arthritis Response to Medication Study (CHARMS), Lucy R. Wedderburn, Wendy Thomson, Cathryn M. Lewis, and Patricia Woo (2012)
    Association of the IL-10 Gene Family Locus on Chromosome 1 with Juvenile Idiopathic Arthritis (JIA)
    in PloS one
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Ebun Omoyinmi, Paola Forabosco,Raja Hamaoui, Annette Bryant, Anne Hinks, Simona Ursu, Childhood Arthritis Prospective Study (CAPS), BSPAR study group,Childhood Arthritis Response to Medication Study (CHARMS), Lucy R. Wedderburn, Wendy Thomson, Cathryn M. Lewis, and Patricia Woo (literal)
Pagina inizio
  • e47673 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 7 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 10 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Immunology and Molecular Pathology, University College London, London, United Kingdom Istututo di Genetica delle Popolazioni, CNR, Sassari, Italy Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom Rheumatology Unit, Institute of Child Health, University College London, London, United Kingdom King's College London, Department of Medical and Molecular Genetics, London, United Kingdom King's College London, MRC SGDP Centre, Institute of Psychiatry, London, United Kingdom University of Freiburg, Germany (literal)
Titolo
  • Association of the IL-10 Gene Family Locus on Chromosome 1 with Juvenile Idiopathic Arthritis (JIA) (literal)
Abstract
  • Background The cytokine IL-10 and its family members have been implicated in autoimmune diseases and we have previously reported that genetic variants in IL-10 were associated with a rare group of diseases called juvenile idiopathic arthritis (JIA). The aim of this study was to fine map genetic variants within the IL-10 cytokine family cluster on chromosome 1 using linkage disequilibrium (LD)-tagging single nucleotide polymorphisms (tSNPs) approach with imputation and conditional analysis to test for disease associations. Methodology/Principal Findings Fifty-three tSNPs were tested for association between Caucasian paediatric cohorts [219 systemic JIA (sJIA), 187 persistent oligoarticular JIA (pOJIA), and 139 extended OJIA (eOJIA) patients], and controls (Wellcome Trust control cohort, WTCCC2). Significant association with sJIA was detected at rs1400986 in the promoter of IL-20 (odds ratio 1.53; 95% CI 1.21-1.93; p=0.0004), but in no other subtypes. Imputation analysis identified additional associated SNPs for pOJIA at IL-20 and IL-24, including a rare, functional, missense variant at IL-24 with a p=0.0002. Penalised logistic regression analysis with HyperLasso and conditional analysis identified several further associations with JIA subtypes. In particular, haplotype analysis refined the sJIA association, with a joint effect at rs1400986 and rs4129024 in intron 1 of MAPKAPK2 (p=3.2E-5). For pOJIA, a 3-SNP haplotype including rs1878672 in intron 3 of IL-10 showed evidence for association (p=0.0018). In eOJIA, rs10863962 (3?UTR of FCAMR) and rs12409577 (intron of IL-19) haplotype showed some evidence of association (p=0.0003). Conclusions This study supports previous association of IL-20 with sJIA. Haplotype analyses provided stronger association signals than single point analyses, while a penalised logistic regression approach also suggested multiple independent association signals. Replication studies are required to confirm or refute these findings. The results indicate that combined effects with unknown/rare variants remain to be characterised in JIA, and represent a possible example of synthetic association in this region. (literal)
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