CONCISE REPORT

TLR4 mutations (Asp299Gly and Thr399Ile) are not associated with ankylosing spondylitis

R Adam¹, R D Sturrock², J A Gracie²

¹ Centre for Rheumatic Diseases, University Department of Medicine, Queen Elizabeth Building, Glasgow Royal Infirmary University Trust, 10 Alexandra Parade, Glasgow G31 2ER, UK
² Section of Rheumatology, Division of Immunology, Inflammation and Infection, Faculty of Medicine, University of Glasgow, Glasgow, UK

Correspondence to:
Correspondence to:
Dr R Adam
RosalindA{at}doctors.org.uk

Background: Immunoregulatory genes and Gram negative gut bacteria are thought to be important in disease expression in ankylosing spondylitis (AS).

Objective: To compare the frequency of two common and functional TLR4 mutations (Asp299Gly, and Thr399Ile) between patients with AS and HLA-B27 healthy controls.

Methods: The TLR4 genotypes of patients and healthy HLA-B27 controls were determined using allele-specific PCR and restriction fragment length polymorphism analysis. Asp299Gly genotype was determined in 193 patients and 125 HLA-B27 positive controls and Thr399Ile genotype in 184 patients and 113 HLA-B27 controls. Allele frequencies were compared using a ² test of association.

Results: 29/193 (15%) patients with AS had a polymorphism in the Asp299 site compared with 18/125 (14.4%) healthy HLA-B27 controls. Of the patients genotyped for the Thr399Ile allele, 29/184 (15.8%) carried the polymorphism compared with 19/113 (16.8%) HLA-B27 controls. No significant difference between the frequencies of the Asp299Gly genotype or the Thr399Ile genotype between patients with AS and healthy HLA-B27 controls was found. No significant difference in allele frequency was found at either site.

Conclusion: Two common TLR4 polymorphisms, which cause a functional deficiency in host immune response to Gram negative bacteria, are not overrepresented in patients with AS.

Abbreviations: AS, ankylosing spondylitis; CD, Crohn’s disease; LPS, lipopolysaccharide; PCR, polymerase chain reaction; TLRs, Toll-like receptors; UC, ulcerative colitis

Keywords: ankylosing spondylitis; Toll-like receptor; TLR4; innate immunity

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