Division of Rheumatology, Hospital Universitario Marqués de Valdecilla, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
Rheumatology (Oxford). 2011 Sep;50(9):1562-8. doi: 10.1093/rheumatology/ker168. Epub 2011 May 17.
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.
Toll 样受体 4（TLR4）的编码变异已被报道与炎症性疾病有关。本研究旨在确定这两种多态性（+896 A/G 和+1196 C/T）是否与 GCA 的易感性和临床特征相关。我们还试图对这些多态性的功能后果进行相关性分析。
采用等位基因特异性 PCR 和限制性片段长度多态性分析对 72 例 GCA 患者和 126 例年龄匹配的对照者进行基因型分析。通过流式细胞术研究外周血单个核细胞中 TLR4 的表达，并通过体外刺激单核细胞来评估 TLR4 功能。
GCA 患者与对照组之间 TLR4（+896 A/G 和+1196 C/T）的等位基因频率或基因型无显著差异。这些患者的临床特征与这些多态性的存在无关。此外，我们没有观察到 TLR4 表达或 TLR4 反应的特定表型与+896 A/G 和+1196 C/T 基因型之间存在关联。
我们的结果不支持这些 TLR4 变异与 GCA 相关。需要进行包括更多患者和来自不同地理起源的患者群体的研究。
