RESEARCH - TLR4 mutations are not associated with ankylosing spondylitis

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Ann Rheum Dis. 2006 Aug;65(8):1099-101.

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

spondylitis.

Adam R, Sturrock RD, Gracie JA.

Centre for Rheumatic Diseases, University Department of Medicine, Queen

Building, Glasgow Royal Infirmary University Trust, 10 andra

Parade, Glasgow G31 2ER, UK. lindA@...

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

chi(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.

PMID: 16837493

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6837493

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