Journal Article

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap

Martin, Paul, Langefeld, Carl D, Flynn, Edward, Worthington, Jane, Cobb, Joanna, Barton, Anne, Glass, David N, Hinks, Anne, Eyre, Stephen, Packham, Jonathon, Thomson, Wendy, Thompson, Susan D, Sudman, Marc

2012

Overview

Objectives Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA. Methods Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings. Results Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort. Conclusions A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,BMJ Publishing Group,Elsevier Limited,BMJ Group
• Subject: Adolescent / Arthritis, Juvenile - diagnosis / Arthritis, Juvenile - genetics / Arthritis, Juvenile - metabolism / Autoimmune diseases / Biological and medical sciences / CD3 Complex - genetics / CD3 Complex - metabolism / Child / Child, Preschool / Children & youth / Clinical and Epidemiological Research / Consortia / Deoxyribonucleic acid / Disease / Disease Progression / Diseases of the osteoarticular system / DNA / Ethics / Gene Frequency / Genetic Predisposition to Disease / Genetic testing / Genome-Wide Association Study / Genomes / Genotype / Health risk assessment / Hospitals / Humans / Inflammatory joint diseases / Interleukin-2 Receptor alpha Subunit - genetics / Interleukin-2 Receptor alpha Subunit - metabolism / Medical sciences / Polymorphism, Single Nucleotide / Principal components analysis / Protein Tyrosine Phosphatase, Non-Receptor Type 2 - genetics / Protein Tyrosine Phosphatase, Non-Receptor Type 2 - metabolism / Rheumatology / Risk factors / Studies / White people