Toll-like Receptor 4 and CD14 Polymorphisms in Ankylosing Spondylitis: Evidence of a Weak Association in Finns

JENNIFER J. POINTON, KAY CHAPMAN, DAVID HARVEY, ANNE-MARIE SIMS, LINDA BRADBURY, KARI LAIHO, MARKKU KAUPPI, KALEVI KAARELA, JAAKKO TUOMILEHTO, MATTHEW A. BROWN, and B. PAUL WORDSWORTH

ABSTRACT.

Objective. To investigate the association of CD14 and Toll-like receptor (TLR4) with ankylosing spondylitis (AS).

Methods. A promoter variant in CD14 and 2 coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies was performed.

Results. In the Finnish study the CD14-260bp T variant showed an association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak association (global p = 0.03), with AS. No associations were seen in the UK based studies or in the metaanalyses.

Conclusion. CD14 and TLR4 showed an association with AS in the Finns only. (First Release July 15 2008; J Rheumatol 2008;35:1609–12)

Key Indexing Terms:

ANKYLOSING SPONDYLITIS
GENETIC STUDIES
IMMUNE SYSTEM

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From the University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford, UK; Diamantina Institute for Cancer, Immunology and Metabolic Medicine (DI), University of Queensland, Brisbane, Australia; Rheumatism Foundation Hospital, Heinola; Department of Musculoskeletal Medicine, Medical School, University of Tampere, Tampere; National Public Health Institute; University of Helsinki, Helsinki; and South Ostrobothnia Central Hospital, Seinäjoki, Finland.

Funded by a program grant from the Arthritis Research Campaign (UK).

J.J. Pointon, DPhil, Research Assistant; K. Chapman, PhD, Botnar Research Fellow; D. Harvey, MSc, Graduate Student; B.P. Wordsworth, MB, FRCP, Professor of Rheumatology, University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre; A-M Sims, DPhil, Research Assistant; L. Bradbury, MSc, Research Nurse, Diamantina Institute for Cancer, Immunology and Metabolic Medicine; M. Kauppi, MD, PhD, Specialist in Internal Medicine and Rheumatology and Senior Lecturer; K. Kaarela, MD, PhD, Chief Rheumatologist, Rheumatism Foundation Hospital, Heinola; K. Laiho, MD, PhD, Senior Rheumatologist, Rheumatism Foundation Hospital, Heinola and Department of Musculoskeletal Medicine, Medical School, University of Tampere; J. Tuomilehto, MD, PhD, Professor of Public Health, National Public Health Institute, University of Helsinki, and South Ostrobothnia Central Hospital; M.A. Brown, MD, FRACP, Professor of Immunogenetics, University of Oxford Institute of Musculoskeletal Medicine and Diamantina Institute.

Address reprint requests to Dr. J.J. Pointon, University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Headington, Oxford, OX3 7LD, UK. E-mail: jennyp@well.ox.ac.uk

Accepted for publication March 14, 2008.

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