RT Journal Article
SR Electronic
T1 No evidence for involvement of the Toll-like receptor 4 (TLR4) A896G and CD14-C260T polymorphisms in susceptibility to ankylosing spondylitis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 235
OP 238
DO 10.1136/ard.2004.021105
VO 64
IS 2
A1 M van der Paardt
A1 J B A Crusius
A1 M H M T de Koning
A1 S A Morré
A1 R J van de Stadt
A1 B A C Dijkmans
A1 A S Peña
A1 I E van der Horst-Bruinsma
YR 2005
UL http://ard.bmj.com/content/64/2/235.abstract
AB 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.