Association between the Interleukin-1 Family Gene Cluster and uveitis in a Spondyloarthritis French cohort

Abstract

Purpose: : Spondyloarthritis (SpA) is a group of articular disorders sharing genetic background. Polymorphisms in the interleukin-1 (IL1) gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of SpA. Here, we examined the association between several of these polymorphisms and the whole SpA. A particular attention was devoted to genotype-phenotype correlations.

Methods: : Eight single-nucleotide polymorphisms (SNPs) located in the IL1 gene cluster were genotyped in 185 independent SpA trios. Family-based association test was computed using the FBAT software. Analysis was carried in SpA, SA, psoriasis and uveitis. A case-control replication study was performed for 4 of the SNPs, in an independent sample of 414 SpA and 264 controls. A combined analysis of both studies was performed.

Results: : The SNP rs2856836 in IL1A was significantly associated with SpA (p = 0.009) and AS (p = 0.010) in family study. More limit significance was achieved with IL1F10.3 (rs3811058) and SpA (p=0.04). The patients without ankylosing of sacroiliitis did not show any association with IL1, while a tendency between IL1F10.3 and uveitis (p=0.04) or psoriasis (P=0.07) was still observed. The case/control study revealed an association between another IL1A variant (rs1894399) and AS (p=0.035), and between IL1F10.3 (rs3811058) and SpA (P=0.041). By combining family and case/control studies an association between AS and IL1A was confirmed (rs1894399, p=0.024), whereas non-AS was more significantly associated with IL1F10.3 (p=0.0043).

Conclusions: : Our study indicates that two regions, including IL1A and IL-1F10 confer risk of SpA. Furthermore, the first locus was associated with ankylosing sponylitis phenotype, whereas the second one was associated with occurrence of uveitis and psoriasis, the most frequent extra-articular manifestations. These our observations suggest that the Interleukin 1-F10 may play a significant role in the physiopathology of uveitis.

Keywords: uveitis-clinical/animal model • genetics • inflammation