Rheumatology Advance Access originally published online on October 4, 2008
Rheumatology 2008 47(12):1768-1770; doi:10.1093/rheumatology/ken374
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Interleukin-1 promoter region polymorphism role in rheumatoid arthritis: a meta-analysis of IL-1B-511A/G variant reveals association with rheumatoid arthritis
1Institute of Musculoskeletal Sciences and 2Cancer Research UK Epidemiology Unit, University of Oxford, Oxford, UK.
Correspondence to: P. Harrison, Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD, UK. E-mail: pille.harrison{at}ndos.ox.ac.uk
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Objectives. IL-1 has a central role mediating inflammation and joint destruction in RA. Single nucleotide polymorphisms (SNPs) and haplotype structure in the promoter region can modulate IL-1 function. This study examined the effects of four common promoter SNPs in the IL-1 region on susceptibility and clinical characteristics of RA in British Caucasian patients and assessed the risk of RA by meta-analysis of published studies.
Methods. Using PCR-based methods, 756 RA patients and 625 healthy controls (HCs) were genotyped for IL-1A (–889 C/A, rs17561), IL-1B (–511 A/G, rs16944), IL-1B (–1464 C/G, rs1143623) and IL-1B (–3737 G/A, rs4848306) SNPs. Further meta-analysis was performed for IL-1B (–511 A/G) incorporating 3712 RA patients and 2331 HC from six association studies.
Results. The IL-1B (–1464 C/G) G allele was found to be less common in the RA group [P = 0.01; odds ratio (OR) 1.24; 95% CI 1.04, 1.48]. There was no association between IL-1 SNPs and the presence of HLA-DRB1 shared epitope, RF or clinical characteristics. Meta-analysis revealed statistically significant association between IL-1B (–511 A/G) and RA (P = 0.02; pooled OR 1.13; 95% CI 1.02, 1.26).
Conclusions. There may be a protective effect in RA from the IL-1B (–1464 C/G) G variant. No direct association between the polymorphisms studied and clinical severity characteristics were observed. Further meta-analysis revealed IL-1B (–511 A/G) to be associated with increased susceptibility to RA.
KEY WORDS: Rheumatoid arthritis, Meta-analysis, Interleukin-1, Interleukin-1A, Interleukin-1B, Association study, Major histocompatibility complex, Radiographic severity, Genetics, Polymorphism
Submitted 1 July 2008;
revised version accepted 18 August 2008.
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