Interleukin-1 promoter region polymorphism role in rheumatoid arthritis: a meta-analysis of IL-1B-511A/G variant reveals association with rheumatoid arthritis.
OBJECTIVE
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.
Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD, UK. pille.harrison@ndos.ox.ac.uk
P
P
Harrison
J J
JJ
Pointon
K
K
Chapman
A
A
Roddam
B P
BP
Wordsworth
D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011859:Radiography
D053583:Interleukin-1beta