Association between the IL-1 family gene cluster and spondyloarthritis.
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).


CONCLUSIONS
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.
Department of Ophthalmology,Institut Cochin (INSERM U1016, CNRS UMR8104 and Université Paris Descartes, Paris, France.
Dominique
D
Monnet
Amir
A
Kadi
Brigitte
B
Izac
Nicolas
N
Lebrun
Franck
F
Letourneur
Elena
E
Zinovieva
Roula
R
Said-Nahal
Gilles
G
Chiocchia
Maxime
M
Breban
D016022:Case-Control Studies; D005192:Family Health; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics* / Q000276:immunology; D007375:Interleukin-1 / Q000235:genetics* / Q000276:immunology; D053582:Interleukin-1alpha / Q000235:genetics* / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D015810:Linkage Disequilibrium; D005810:Multigene Family / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology
C508584:IL1A protein, human; C508585:IL1B protein, human; C430241:IL1F10 protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053582:Interleukin-1alpha; D053583:Interleukin-1beta