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TLR4 polymorphism is not associated with biopsy proven giant cell arteritis


Dunstan, E and Lester, S and Rischmueller, M and Chan, H and Hewitt, AW and Hill, C, TLR4 polymorphism is not associated with biopsy proven giant cell arteritis, Clinical and Experimental Rheumatology, 32, (Suppl. 82) pp. S26-S29. ISSN 0392-856X (2014) [Refereed Article]


Objective: 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).

Conclusion: There is no evidence of an association between TLR4 polymorphism and susceptibility to GCA.

Item Details

Item Type:Refereed Article
Keywords:Case-control studies; Giant cell arteritis; Polymorphism; Vasculitis
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:96452
Year Published:2014
Web of Science® Times Cited:4
Deposited By:Medicine
Deposited On:2014-11-06
Last Modified:2017-11-03

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