Department of Rheumatology and Immunology of the Affiliated Hospital, North Sichuan Medical College, China.
PLoS One. 2013 May 30;8(5):e64845. doi: 10.1371/journal.pone.0064845. Print 2013.
The toll-like receptor (TLR)4-interleukin1β (IL1β) signaling pathway is involved in the monosodium urate (MSU)-mediated inflammation. The aim of this present study was to determine whether the TLR4 gene rs2149356 SNP is associated with gouty arthritis (GA) susceptibility and whether rs2149356 SNP impacts the TLR4-IL1β signaling pathway molecules expression.
The rs2149356 SNP was detected in 459 GA patients and 669 control subjects (containing 459 healthy and 210 hyperuricemic subjects). Peripheral blood mononuclear cells (PBMCs) TLR4 mRNA and serum IL1β were measured in different genotype carriers, and correlations between TLR4 gene SNP and TLR4 mRNA, IL1β were investigated. The frequencies of the genotype and allele were significantly different between the GA and control groups (P<0.01, respectively). The TT genotype was associated with a significantly increased risk of GA (OR = 1.88); this finding was not influenced by making adjustments for the components of possible confounders (adjusted OR = 1.96). TLR4 mRNA and IL1β were significantly increased in the TT genotype from acute GA patients (P<0.05, respectively), and lipids were significantly different among three genotypes in the GA patients (P<0.05, respectively).
The TLR4 gene rs2149356 SNP might be associated with GA susceptibility, and might participate in regulating immune, inflammation and lipid metabolism. Further studies are required to confirm these findings.
Toll 样受体 (TLR)4-白细胞介素 1β (IL1β) 信号通路参与单钠尿酸盐 (MSU) 介导的炎症。本研究旨在确定 TLR4 基因 rs2149356 单核苷酸多态性是否与痛风性关节炎 (GA) 易感性相关，以及 rs2149356 单核苷酸多态性是否影响 TLR4-IL1β 信号通路分子的表达。
在 459 例 GA 患者和 669 例对照者（包含 459 例健康者和 210 例高尿酸血症者）中检测 rs2149356 单核苷酸多态性。在不同基因型携带者中测量外周血单个核细胞 (PBMC) TLR4 mRNA 和血清 IL1β，并研究 TLR4 基因 SNP 与 TLR4 mRNA、IL1β 之间的相关性。GA 组和对照组的基因型和等位基因频率存在显著差异（P<0.01，分别）。TT 基因型与 GA 的发病风险显著增加相关（OR = 1.88）；这一发现不受对可能混杂因素组成部分进行调整的影响（调整 OR = 1.96）。急性 GA 患者 TT 基因型的 TLR4 mRNA 和 IL1β 显著增加（P<0.05，分别），GA 患者三种基因型之间的脂质水平存在显著差异（P<0.05，分别）。
TLR4 基因 rs2149356 单核苷酸多态性可能与 GA 易感性相关，并可能参与调节免疫、炎症和脂质代谢。需要进一步的研究来证实这些发现。
