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

Comparative Study

. 2003 May-Jun;21(3):340-2.

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Comparative Study

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

R Kilding et al. Clin Exp Rheumatol. 2003 May-Jun.

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 Histocompatibility 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-->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.

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