European Journal of Rheumatology
Original Article

IL-1A gene variation in relation to cytokine levels and clinical characteristics in ankylosing spondylitis

1.

Department of Rheumatology, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Australia

2.

Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway

3.

Department of Rheumatology, University Hospital North Norway, Tromsø, Norway

Eur J Rheumatol 2019; 6: 67-70
DOI: 10.5152/eurjrheum.2018.18150
Read: 119 Downloads: 21 Published: 03 September 2019

Abstract

Objective: Variations in the IL-1 alpha (IL-A) gene increase the risk for ankylosing spondylitis (AS), but the pathway underlying this association is not fully understood. As IL-1A is primarily a regulatory cytokine, we investigated the influence of IL-1A gene variation on disease severity and cytokine expression in AS.

 

Methods: This was a cross sectional study of tumor necrosis factor inhibitors (TNFi)-naïve AS patients (n=334, 90% B27 +, age 45 years) fulfilling the modified New York criteria. We recorded demographics, clinical findings, spinal mobility, Bath AS Functional Index (BASFI), and routine lab findings. IL-1A genotyping for three AS-associated single nucleotide polymorphism (SNP; rs2856836, rs17561 and rs1894399) was performed using Taqman RT-PCR, with TNF, IL-6, IL-17A, and IL-23 levels measured using ELISA. Genotypic associations included logistic regression analysis for genotype (codominant model) and global haplotype (threshold 5%) associations with cytokine levels and clinical features.

 

Results: The three variants were in near complete linkage disequilibrium and formed two only common haplotypes (ACC 67%, GAT 33%). The levels for TNF, IL-6, IL-17A, IL-23, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were similar across genotypes and haplotypes (all p-values >0.4) as were the measures for spinal mobility and BASFI. The TAQ haplotype showed a borderline significant trend with reduced heart disease and mortality during follow-up.

 

Conclusion: IL-1A gene cluster variations do not have an impact on the clinical disease measures or cytokine levels in AS, suggesting that IL-1A has no direct role in AS.

 

Cite this article as: Nossent JC, Sagen-Johnsen S, Bakland G. IL-1A gene variation in relation to cytokine levels and clinical characteristics in ankylosing spondylitis. Eur J Rheumatol 2019; 6(2): 64-7.

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ISSN2147-9720 EISSN 2148-4279