Lack of association or interactions between the IL-4, IL-4Ralpha and IL-13 genes, and rheumatoid arthritis.
BACKGROUND
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-4Ralpha and IL-13 genes in RA, including an examination of epistasis.


METHODS
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-4Ralpha (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.


RESULTS
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-4Ralpha.


CONCLUSIONS
These results indicate that common variants of the IL-4/IL-13 pathway do not significantly contribute to RA susceptibility and radiological severity.
Marinou
Ioanna
I
Section of Musculoskeletal Sciences, School of Medicine & Biomedical Sciences, The University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK.
Till
Simon H
SH
Moore
David J
DJ
Wilson
Anthony G
AG
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics
D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4