Lack of association between Toll-like receptor 4 gene polymorphisms and giant cell arteritis

Abstract

Coding variants in Toll-like receptor 4 (TLR4) have been reported to be associated with inflammatory diseases. The aim of this study was to determine whether two of these polymorphisms (+896 A/G and +1196 C/T) are associated with susceptibility and clinical features of GCA. We also attempted to correlate the functional consequences of these polymorphisms. A total of 72 patients with GCA and 126 age-matched controls were genotyped using allele-specific PCR and restriction fragment length polymorphism analysis. TLR4 expression was studied on peripheral blood mononuclear cells by flow cytometry and TLR4 function was assessed by stimulating monocytes in vitro with a specific ligand. There was no significant difference in allele frequency or genotype of TLR4 (+896 A/G and +1196 C/T) between GCA patients and controls. The clinical characteristics of these patients were unrelated to the presence of these polymorphisms. Furthermore, we did not observe an association with TLR4 expression or a distinct phenotype of TLR4 response with the +896 A/G and +1196 C/T genotypes. Our results do not support the association of these TLR4 variants with GCA. Studies including a larger number of patients and patient populations from different geographical origin are needed.