Objective: Interleukin-1 (IL-1) has been implicated in the pathogenesis of several rheumatic inflammatory diseases, including adult-onset Still's disease (AOSD) and systemic-onset juvenile idiopathic arthritis (SoJIA). Several clinical trials also suggest that anakinra, a human recombinant interleukin-1 receptor antagonist (IL-1Ra), is effective in patients with AOSD and SoJIA. We have therefore investigated whether IL-1beta and IL-1Ra gene polymorphisms are associated with the development and clinical features of AOSD.
Methods: Genomic DNA was isolated from 83 AOSD patients and 144 healthy controls. Genotyping of the two IL-1beta gene (IL-1B+3954 and IL-1B-511) polymorphisms was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Genotyping of the IL-1Ra gene (intron 2, VNTR) polymorphism was performed using PCR-based analysis. To compare genotype and allele frequencies, the chi2-test or Fisher's exact test was used. Haplotype frequencies and pairwise linkage disequilibrium were also estimated. A p-value <0.05 was considered significant.
Results: There were no significant differences in the genotype and allele frequencies of the IL-1beta and IL-1Ra gene polymorphisms. No differences were also found in the IL-1 gene cluster haplotypes between both groups. IL-1 gene cluster polymorphisms had no effect on the clinical course and joint involvement pattern. Nevertheless, the IL-1B-511 and IL-1RN (VNTR) polymorphic sites were in linkage disequilibrium.
Conclusion: These results suggest that IL-1beta and IL-1Ra gene polymorphisms are not associated with the development and clinical features of AOSD in Korean patients.