Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: The objective of this study was to evaluate single nucleotide polymorphisms (SNPs) involved in TNFα signaling, NF-κB activation, interferon-γ signaling, or pattern recognition receptor signaling pathways (TLRs and inflammasome) and their association with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) susceptibility. The genotyped SNPs have known functional effects or previously reported associations with chronic autoimmune disease.
Methods: In a cross-sectional study, we genotyped 53 SNPs in 709 AS patients and 58 SNPs in 538 RA patients from Denmark. Prospectively collected clinical data were obtained from the DANBIO registry. Genotype distributions among cases were compared with 796 population-based controls. Odds ratios for minor allele carriers among cases adjusted for gender and age were calculated assuming additive genetic effects. Correction for multiple testing was performed using false discovery rate (FDR), and associations with FDR q-values <0.1 were considered significant.
Results: We find a decreased risk of AS in minor allele carriers of two SNPs in TNF (rs1800629: odds ratio(OR)=0.59, 95% confidence interval(CI): 0.47-0.74, p=3*10-6, q=1*10-4; rs361525: OR=0.48, CI: 0.31-0.75, p=0.001, q=0.02), and of IL23R rs11209026 (OR= 0.60, CI: 0.43-0.85, p=0.004, q=0.05). Carriers of the minor allele of TNFRSF1A rs4149570 (OR=1.32, CI: 1.14-1.54, p= 3*10-04, q=0.007) had increased risk of AS. Among RA patients, no statistically significant associations were observed. However, a previously reported RA risk allele in PTPN22(rs2476601) showed a similar trend in this cohort (OR=1.39, CI: 1.06-1.82, p=0.016, q=0.3).
Conclusion: In a Danish population, this study confirms a previously reported locus in the interleukin-23 receptor (rs11209026) as less common in AS patients, and identifies genetic variation in TNFα (rs1800629, rs361525) and TNF receptor-1 (rs4149570) as putative loci associated with AS. Among RA patients, no SNPs reached significant association but the previously reported risk allele PTPN22 rs2476601 showed a borderline association with disease susceptibility.
To cite this abstract in AMA style:Sode J, Vogel U, Bank S, Andersen PS, Lund Hetland M, Locht H, Heegaard NHH, Andersen V. Genetic Variants in TNF, TNFRSF1A, and IL23R Are Associated with Risk of Ankylosing Spondylitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/genetic-variants-in-tnf-tnfrsf1a-and-il23r-are-associated-with-risk-of-ankylosing-spondylitis/. Accessed October 24, 2021.
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