Association of interleukin-4 and interleukin-1B gene variants with Larsen score progression in rheumatoid arthritis

Objective. To perform a genetic association study using markers in the interleukin-1 (IL-1) gene cluster and the IL-4/IL-4 receptor system genes, seeking evidence for involvement in the onset or the erosive outcome of rheumatoid arthritis (RA). Methods. We tested the allelic distribution of IL-1A (+4845), IL-1B (-511), IL-1B (+3954), IL-1RN (+2018), IL-4 variable number of tandem repeat (VNTR), and IL-4R (+1902) in 233 patients with RA, 99 with polymyalgia rheumatica, and 148 ethnically matched controls. We analyzed the frequency of these gene variants in respect to presence of disease, but also to the degree of radiologic erosions (Larsen score) as a function of disease duration in 157 patients who had available radiographs of both hands. Results. None of the 6 genetic polymorphisms was significantly different in frequency between RA patients and healthy controls or patients with polymyalgia rheumatica. Among RA patients, the rarer (#2) alleles of IL-4 VNTR and IL-1B (-511) were both associated with a milder Larsen score progression: The slope of Larsen progression in the rare allele groups diverged significantly from those of the frequent allele groups after approximately 20 years of disease duration (P < 0.001). Conclusion. None of the markers tested were shown to be associated with increased or decreased risk of RA. The rarer alleles of IL-4 VNTR and IL-1B (-511) appear to be associated with a less severe course in RA of long duration.