ab21308

A biologically important single nucleotide polymorphism within the toll-like receptor-4 gene is not associated with rheumatoid arthritis

R. Kilding, M. Akil, S. Till, R. Amos, J. Winfield, M.M. Iles, A.G. Wilson

Medicine, Royal Hallamshire Hospital, Sheffield, United Kingdom.

ABSTRACT
Background
Rheumatoid arthritis (RA) is a heterogeneous condition affecting 1-2% of the population. Genetics account for 30% of disease susceptibility, with one third arising from the Major Histocompatibilty Complex. The toll-like receptor 4 (TLR-4) gene which has been mapped to chromosome 9 (9q32-q33) is involved in innate immune recognition with subsequent proinflammatory cytokine release including TNF. A single nucleotide polymorphism (+896A Õ G) resulting in the amino acid substitution (Asp299Gly) has been shown to interrupt TLR-4 mediated signalling.

Objective
We sought to determine if this TLR-4 polymorphism influences susceptibility to rheumatoid arthritis.

Methods
DNA was extracted from 879 healthy controls and 212 rheumatoid arthritis patients recruited from the north of England. Genotyping was performed using a 5' nuclease Taqman allelic discrimination assay. Allele frequencies were compared between the two groups. We also examined whether an association existed in non-carriers of the DRB1 shared epitope alleles.

Results
The frequency of the rare allele was 5.9% in the controls and 7% in the patients. Comparison of rare allele carriage between controls and patients revealed no significant difference p = 0.13. This was also the case in shared epitope negative individuals p = 0.92.

Conclusion
The TLR-4 +896 polymorphism does not appear to influence susceptibility to rheumatoid arthritis.

Key words
Toll-like receptor 4, polymorphism, rheumatoid arthritis, genetics.

Please address correspondence to: Dr R. Kilding, Division of Genomic Medicine, Royal Hallamshire Hospital, Sheffield S10 2JF, United Kingdom.
E-mail: r.kilding@sheffield.ac.uk