Background/Purpose: Spondyloarthritis (SpA) is a group of articular disorders sharing genetic background. Single-nucleotide polymorphisms (SNP) of the interleukin 23 receptor (IL23R) gene have been reproducibly reported as associated with ankylosing spondylitis (AS) a subset of SpA, defined by advanced radiographic sacroiliitis. Here, we examined the association between several SNPs in the IL23R gene and SpA as a whole. A particular attention was devoted to genotype-phenotype correlations.

Methods:  Eight single-nucleotide polymorphisms (SNPs) located in the IL23R gene were genotyped in a collection of 414 independent French SpA patients and 264 healthy controls. In addition, the most significantly associated polymorphism rs11209026 (Arg381Gln) was genotyped in 156 multiplex families of SpA and in 136 independent trios. Association analyses were carried using UNPHASED, in SpA as a whole group, and then separately in AS and non-radiographic SpA (non-AS) patients.

Results: Strong association with AS was observed in the 3 datasets (case/control, familial and trios) with the non-synonymous polymorphism rs11209026 Arg381Gln (P=2.86 x 10^-3 P=4.59 x 10^-3 and p=0.02, respectively). In contrast, such association was not detected with the non-AS group (P=0.878, p=0.65 and p=1). Furthermore, association with this polymorphism was significantly different between the AS and non-AS patients in both studies (P=2.5 x 10^-3).

Conclusion:  Our results confirm that IL23R polymorphisms are associated with SpA, either in sporadic or in familial cases. However, phenotypic analysis revealed that association with Arg381Gln polymorphism is restricted to the AS subtype, suggesting that IL23R could influence the phenotypic expression of SpA by promoting ankylosis.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-non-synonymous-polymorphism-il23r-arg381gln-is-associated-with-ankylosis-in-spondyloarthritis/