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

Abstract

Objective: Variations in the IL-1 alpha (IL-A) gene increase the risk for ankylosing spondylitis (AS), butthe pathway underlying this association is not fully understood. As IL-1A is primarily a regulatorycytokine, 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-1Agenotyping for three AS-associated single nucleotide polymorphism (SNP; rs2856836, rs17561 andrs1894399) was performed using Taqman RT-PCR, with TNF, IL-6, IL-17A, and IL-23 levels measuredusing ELISA. Genotypic associations included logistic regression analysis for genotype (codominantmodel) 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 borderlinesignificant 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 orcytokine levels in AS, suggesting that IL-1A has no direct role in AS.