OBJECTIVE: Spondyloarthritis (SpA) is a group of inflammatory articular disorders sharing a genetic background. The nonsynonymous single-nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) in the IL23R gene has reproducibly been shown to be associated with ankylosing spondylitis (AS). We undertook this study to examine the association between rs11209026 and SpA as a whole, with particular attention devoted to genotype/phenotype correlation. METHODS: The SNP rs11209026 was genotyped in a French cohort of 415 patients/372 controls, with replication analysis performed in 383 "trios," each consisting of 1 patient with SpA and both parents. Association analysis was carried out in SpA as a whole group and then separately in AS and non-AS patients. Phenotype/genotype correlations were examined using logistic regression analysis. RESULTS: A significant association between rs11209026 and SpA overall was identified only in the familial data set (odds ratio 0.57, P=0.028). Strong association with AS was observed in both the case-control and familial data sets (P=4.5×10(-4) and P=4.0×10(-3), respectively). In contrast, such association was not detected in the non-AS group. Furthermore, rs11209026 frequency was significantly different between AS and non-AS patients (P=1.5×10(-3)). Phenotype/genotype correlation study revealed that both radiographic sacroiliitis and early age at onset were independently associated with a lower frequency of the rare protective rs11209026 allele A in patients (P=9×10(-3) and P=8×10(-3), respectively). CONCLUSION: Our study replicated the robust association between rs11209026 and AS in the French population. However, such association was restricted to AS, as compared to SpA without radiographic sacroiliitis. The fact that it was independently conditional on radiographic sacroiliitis and age at onset suggests that rs11209026 could affect disease severity rather than susceptibility.
OBJECTIVE:Spondyloarthritis (SpA) is a group of inflammatory articular disorders sharing a genetic background. The nonsynonymous single-nucleotide polymorphism (SNP) rs11209026 (Arg381Gln) in the IL23R gene has reproducibly been shown to be associated with ankylosing spondylitis (AS). We undertook this study to examine the association between rs11209026 and SpA as a whole, with particular attention devoted to genotype/phenotype correlation. METHODS: The SNP rs11209026 was genotyped in a French cohort of 415 patients/372 controls, with replication analysis performed in 383 "trios," each consisting of 1 patient with SpA and both parents. Association analysis was carried out in SpA as a whole group and then separately in AS and non-AS patients. Phenotype/genotype correlations were examined using logistic regression analysis. RESULTS: A significant association between rs11209026 and SpA overall was identified only in the familial data set (odds ratio 0.57, P=0.028). Strong association with AS was observed in both the case-control and familial data sets (P=4.5×10(-4) and P=4.0×10(-3), respectively). In contrast, such association was not detected in the non-AS group. Furthermore, rs11209026 frequency was significantly different between AS and non-AS patients (P=1.5×10(-3)). Phenotype/genotype correlation study revealed that both radiographic sacroiliitis and early age at onset were independently associated with a lower frequency of the rare protective rs11209026 allele A in patients (P=9×10(-3) and P=8×10(-3), respectively). CONCLUSION: Our study replicated the robust association between rs11209026 and AS in the French population. However, such association was restricted to AS, as compared to SpA without radiographic sacroiliitis. The fact that it was independently conditional on radiographic sacroiliitis and age at onset suggests that rs11209026 could affect disease severity rather than susceptibility.