No evidence for involvement of the Toll-like receptor 4 (TLR4) A896G and CD14-C260T polymorphisms in susceptibility to ankylosing spondylitis.
OBJECTIVE
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.
van der Paardt
M
M
Jan van Breemen Institute, VU University Medical Centre, 1007 MB Amsterdam, the Netherlands.
Crusius
J B A
JB
de Koning
M H M T
MH
Morré
S A
SA
van de Stadt
R J
RJ
Dijkmans
B A C
BA
Peña
A S
AS
van der Horst-Bruinsma
I E
IE
D000328:Adult; D000368:Aged; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors