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No evidence for involvement of the Toll-like receptor 4 (TLR4) A896G and CD14-C260T polymorphisms in susceptibility to ankylosing spondylitis
  1. M van der Paardt1,
  2. J B A Crusius2,
  3. M H M T de Koning1,
  4. S A Morré2,
  5. R J van de Stadt1,
  6. B A C Dijkmans1,4,
  7. A S Peña2,3,
  8. I E van der Horst-Bruinsma4
  1. 1The Jan van Breemen Institute
  2. 2the Laboratory of Immunogenetics
  3. 3the Department of Gastroenterology
  4. 4and the Department of Rheumatology, VU University Medical Centre, Amsterdam, the Netherlands
  1. Correspondence to:
    Dr I E van der Horst-Bruinsma
    VU University Medical Centre, Department of Rheumatology, Room 4A-42, PO Box 7057, 1007 MB Amsterdam, the Netherlands; secr.reumatologievumc.nl

Abstract

Objectives: Ankylosing spondylitis (AS) is a multifactorial and polygenic disease. Apart from HLA, other genes very probably play a role in disease susceptibility. Indigenous bacteria of the gastrointestinal flora appear to play a role in the pathogenesis of the disease; therefore, genes controling the innate and acquired immune response are good candidates to study disease susceptibility. CD14 and Toll-like receptor 4 (TLR4) are key receptors for the sensing of bacteria. The CD14 C-260T and TLR4 A896G single nucleotide polymorphims are associated with aberrant signal transduction for bacterial agonists.

Methods: The distribution of the CD14 C-260T and TLR4 A896G polymorphisms was studied in genomic DNA from 113 unrelated white Dutch AS patients and 170 ethnically matched healthy controls. The diagnosis of AS was made according to the modified New York criteria. The CD14 C-260T and TLR4 A896G polymorphisms were genotyped by PCR-RFLP methods.

Results: No significant differences were found between patients and controls in the frequencies of the carriership of the less frequent CD14-260T allele (odds ratio 0.65; 95% confidence interval 0.37 to 1.15) or the TLR4 896G allele (1.68; 0.67 to 4.19).

Conclusions: There is no evidence for involvement of the CD14 C-260T or TLR4 A896G polymorphisms in susceptibility to AS. An important role of bacteria and genetic predisposition of the innate immune system in cases of AS cannot be excluded by these findings. Therefore, studies of the surprisingly highly polymorphic candidate genes in this field should be continued.

  • AS, ankylosing spondylitis
  • CD, Crohn’s disease
  • HSP, heat shock protein
  • LBP, lipopolysaccharide binding protein
  • LPS, lipopolysaccharide
  • NF, nuclear factor
  • SNP, single nucleotide polymorphism
  • TLR, Toll-like receptor
  • UC, ulcerative colitis
  • ankylosing spondylitis
  • Toll-like receptor 4
  • CD14
  • polymorphisms
  • innate immunity
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