Background/Purpose: Ankylosing spondylitis (AS) is an inflammatory disease affecting spine which may lead to new bone formation and disability. However, the radiographic severity of AS shows great variance. The genetic determinants for the new bone formation and for this great variance have not been fully understood yet. By using a well-categorized group of patients representing two extreme ends of AS radiographic severity, we aimed to determine the effects of interleukin-23 receptor (IL23R), bone morpogenetic protein-6 (BMP6) and prostaglandin endoperoxide synthase-1 (PTGS1) gene variants on radiographic severity of AS.

Methods: rs11209026 (IL23R), rs1235192 and rs270378 (BMP6), and rs1236913 (PTGS1) single nucleotide polymorphisms (SNPs) were genotyped in 241 AS patients (F/M=97/144, mean age 42.0±11.0 years, 60.6% HLA-B27[+]) fulfilling the modified New York criteria.  Patients were classifed as mild and severe radiographic AS according to modified Stoke AS spinal score (mSASSS). Mild AS is defined as having mSASSS of “0” despite ≥10 years of disease duration. Whereas severe AS is defined as having mSASSS of >20 (without counting scores with “1”) regardless of the disease duration.

Results: Seventy (29%) and 171 (71%) patients were classified as severe and mild radiographic AS, respectively (mean mSASSS 48.2±17.3 vs 0, P<0.0001).  Severe AS patients were mainly male and significantly older, had longer disease duration, more extra-articular and coxofemoral joint involvement, smoking rates, HLA-B27 positivity and ever TNFi usage. The genotype distributions and allele frequencies of the 4 SNPs were not different in severe group compared to mild group. After adjustment for clinical differences between two groups by logistic regression analysis none of the alleles in those SNPs were found to be associated with radiographic severity of the AS (Table 1). The genotype frequencies also did not change when groups were categorized according to gender and HLA-B27 status. However, HLA-B27 was associated with radiographic severity only in male patients (OR=3.23, 95% CI [1.11 to 9.41], P=0.032). No association with these SNPs and other clinical manifestations of AS, coxofemoral joint involvement, uveitis and enthesitis, could be demonstrated. Severe group patients had higher CRP levels, likewise patients with elevated CRP had higher mSASSS scores (22.1±26.9 vs 10.4±22.4, P=0.001). However no difference was identified.in genotype distributions and allele frequencies of patients with and without elevated CRP.

Conclusion: In a radiographically well-categorized AS cohort IL23R rs11209026, BMP6 rs1235192 and rs270378 and PTGS1rs1236913 SNPs are not found to be associated with radiographic severity of AS. HLA-B27 is associated with radiographic severity only in male AS patients.

Table 1. The distribution of allele frequencies of IL23R, BMP6 and PTGS1 SNPs of mild and severe radiographic AS patients*

*Values are provided as n (%). ^ǂ Risky allele

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/associations-of-il23r-bmp6-and-ptgs1-polymorphisms-with-radiographic-severity-of-ankylosing-spondylitis/