Subtype specific genetic associations for juvenile idiopathic arthritis: ERAP1 with the enthesitis related arthritis subtype and IL23R with juvenile psoriatic arthritis.


Hinks, A; Martin, P; Flynn, E; Eyre, S; Packham, J; Childhood Arthritis Prospective Study-CAPS, ; BSPAR Study Group, ; Barton, A; Worthington, J; Thomson, W; , COLLABORATORS; Baildam, E; Brown, L; Buckley, J; Chieng, A; Davidson, J; Eltringham, M; Foster, H; Friswell, M; Janet, GM; Gilbert, P; Hyrich, K; Jones, J; Lal, S; Lay, M; Lydon, C; Meijer, A; Price, V; Sim, J; Todd, M; Ward, P; Wedderburn, L; 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; (2011) Subtype specific genetic associations for juvenile idiopathic arthritis: ERAP1 with the enthesitis related arthritis subtype and IL23R with juvenile psoriatic arthritis. Arthritis research & therapy, 13 (1). R12. ISSN 1478-6354 DOI: https://doi.org/10.1186/ar3235

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Abstract

Juvenile idiopathic arthritis (JIA) is an umbrella term for all chronic childhood arthropathies and can be divided into seven subtypes. It includes the enthesitis related arthritis (ERA) subtype which displays symptoms similar to ankylosing spondylitis (AS) and juvenile-onset psoriatic arthritis which has similarities to psoriatic arthritis (PsA) and psoriasis (Ps). We, therefore, hypothesized that two well-established susceptibility loci for AS and Ps, ERAP1 and IL23R, could also confer susceptibility to these JIA subtypes. Single nucleotide polymorphisms (SNPs) in ERAP1 (rs30187) and IL23R (rs11209026) were genotyped in JIA cases (n = 1,054) and healthy controls (n = 5,200). Genotype frequencies were compared between all JIA cases and controls using the Cochrane-Armitage trend test implemented in PLINK. Stratified analysis by ILAR subtype was performed. The ERA subtype showed strong association with ERAP1 SNP (P trend = 0.005). The IL23R SNP showed significant association in the PsA subtype (P trend = 0.04). The SNPs were not associated with JIA overall or with any other subtype. We present evidence for subtype specific association of the ERAP1 gene with ERA JIA and the IL23R gene with juvenile-onset PsA. The findings will require validation in independent JIA datasets. These results suggest distinct pathogenic pathways in these subtypes.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID: 21281511
Web of Science ID: 289523500023
URI: http://researchonline.lshtm.ac.uk/id/eprint/2901261

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