Lack of association or interactions between the IL-4, IL-4Rα and IL-13 genes, and rheumatoid arthritis
Section of Musculoskeletal Sciences, School of Medicine & Biomedical Sciences, The University of Sheffield, Royal Hallamshire Hospital, Beech Hill road, Sheffield S10 2RX, UK
Arthritis Research & Therapy 2008, 10:R80 doi:10.1186/ar2454Published: 14 July 2008
A feature of rheumatoid arthritis (RA) is an imbalance between proinflammatory and anti-inflammatory cytokines. Several recent studies have implicated polymorphism in the IL-4 signalling pathway in the development of erosive RA. The aim of the present study was to investigate the role of polymorphism in the IL-4, IL-4Rα and IL-13 genes in RA, including an examination of epistasis.
A total of 965 Caucasian patients with RA (cases) and 988 healthy control individuals (controls) were genotyped for five variants in the IL-4/IL-13 gene cluster (5q31.1) and two functional variants IL-4Rα (16p12.1). Individual genotype and haplotype frequencies were compared between cases and controls. The odd ratios were calculated with asymptotic 95% confidence intervals, and P values less than 0.05 were considered statistically significant. The potential association with radiological joint damage was also examined. Potential gene interactions were assessed using both stratified analysis and the linkage disequilibrium-based statistic.
Genotype, allele and haplotype frequencies were equally distributed between RA cases and controls. Similarly, no association was detected between these variants and modified Larsen scores. Furthermore, no evidence of epistasis was detected between IL-4 or IL-13 genotypes and IL-4Rα.
These results indicate that common variants of the IL-4/IL-13 pathway do not significantly contribute to RA susceptibility and radiological severity.