TLR4 polymorphism is not associated with biopsy proven giant cell arteritis.

ABSTRACT

OBJECTIVES: Giant cell arteritis (GCA) is a systemic inflammatory vasculitis affecting the elderly. It primarily affects medium and large arteries of the head and neck and can cause stroke and blindness. The cause of GCA is unknown; however both genetic and environmental factors are likely to be involved. TLR4 is implicated in the pathogenesis of GCA, however previous studies, examining the association between GCA and two TLR4 single nucleotide polymorphisms (SNPs), have reported conflicting results. The aim of this study was to determine the association between GCA and range of SNPs spanning the TLR4 gene sequence. METHODS: A case-control genetic study was performed using DNA from Australian biopsy proven GCA patients (n=139) and population controls (n=130). Samples were genotyped for 8 SNPs tagging common variation across TLR4. These SNPs included rs4986790 (+896A/G, Asp299Gly) and rs4986791 (+1196C/T) which have been previously studied in GCA. Allelic and haplotypic variation was analysed by logistic regression assuming an additive genetic model. A random effects meta-analysis of the association between GCA and rs4986790 was performed utilising data from three previous studies. RESULTS: rs4986790 and rs4986791 are in strong linkage disequilbrium and tag one of the five common TLR4 haplotypes identified. No associations were observed between TLR4 SNPs and/or haplotypes and GCA. A meta-analysis, comprising 577 GCA patients and 1153 controls, did not confirm an association between GCA and rs4986790 (OR 1.29, 95% CI 0.86, 1.92, p=0.22). CONCLUSIONS: There is no evidence of an association between TLR4 polymorphism and susceptibility to GCA.