TY - JOUR
T1 - IL-1A gene variation in relation to cytokine levels and clinical characteristics in ankylosing spondylitis
AU - Nossent, Johannes C.
AU - Sagen-Johnsen, Sylvia
AU - Bakland, Gunnstein
PY - 2019/4
Y1 - 2019/4
N2 - 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)-naive 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.
AB - 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)-naive 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.
KW - Ankylosing spondylitis
KW - IL1A
KW - SNP
KW - spinal function
KW - cytokines
KW - SINGLE NUCLEOTIDE POLYMORPHISMS
KW - COMPLEX MEMBERS
KW - ASSOCIATION
KW - SUSCEPTIBILITY
KW - CLUSTER
KW - DISEASE
U2 - 10.5152/eurjrheum.2018.18150
DO - 10.5152/eurjrheum.2018.18150
M3 - Article
C2 - 31365338
SN - 2147-9720
VL - 6
SP - 67
EP - 70
JO - European Journal of Rheumatology
JF - European Journal of Rheumatology
IS - 2
ER -