Objective Spondyloarthritis is a group of articular disorders sharing a genetic background. Polymorphisms in the IL-1 gene cluster have previously been associated with ankylosing spondylitis (AS), a subset of spondyloarthritis. This study examined the association between several of these polymorphisms and the whole spondyloarthritis. Particular attention was devoted to genotype–phenotype correlations.
Methods Seven single-nucleotide polymorphisms (SNP) and a variable number tandem repeat located in the IL-1 gene cluster were genotyped in 185 independent spondyloarthritis trios. Family-based association test (FBAT) was computed using the FBAT software. Analysis was carried in spondyloarthritis as a whole and also in AS. A case–control replication study was performed for four of the SNP, in an independent sample of 414 spondyloarthritis and 264 controls. A combined analysis of both studies was performed.
Results The SNP rs2856836 in IL1A was significantly associated with spondyloarthritis (p=0.009) and AS (p=0.010) in the family study. The case–control study revealed an association between another IL1A variant (rs1894399) and AS (p=0.035), and between IL1F10.3 (rs3811058) and spondyloarthritis (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). Family-based and case–control studies revealed significant association between the two most frequent haplotypes combining the four SNP of the replication study and both spondyloarthritis (p=0.0054 and p=0.038) and AS phenotypes (p=0.018 and 0.0036).
Conclusion This study is the first to demonstrate an association between several polymorphisms located in the IL-1 gene cluster and spondyloarthritis as a whole. The IL1A locus was strongly associated with AS phenotype, whereas IL1F10 was associated with non-AS.
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DM and AK contributed equally to the work.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was approved by the local ethics committees of Cochin Hospital (Paris, France) and of Ambroise Paré Hospital (Boulogne Billancourt, France).
Provenance and peer review Not commissioned; externally peer reviewed.
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