Unidad de Investigación, Hospital Juárez de México, Av. Instituto, Politécnico Nacional No. 5160, DelegaciónGustavo A. Madero, C.P. 07760, Mexico City, Mexico.
Servicio de Reumatología, Hospital Juárez de México, Mexico City, Mexico.
Mol Biol Rep. 2021 Apr;48(4):3561-3565. doi: 10.1007/s11033-021-06371-4. Epub 2021 May 3.
Toll-like receptor (TLR)-mediated signaling pathways induce a proinflammatory microenvironment to eradicate pathogens. However, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), TLRs can promote chronic inflammation. It has been shown that some TLR4 and TLR9 single nucleotide polymorphisms (SNPs) are risk factors for RA and SLE, but these findings have not been replicated in all populations; thus, results are inconclusive. We evaluated the TLR4 Asp299Gly, Thr399Ile, - 1892G/A SNPs, and the TLR9 Pro545Pro SNP to assess potential associations with RA and SLE in Mexican patients. This study included 474 patients with RA, 283 patients with SLE, and 424 healthy controls. We used a 5' nuclease allelic discrimination assay to genotype individuals for the four TLR4 and TLR9 polymorphisms. We found that the genotype or allelic frequencies of the TLR4 Asp299Gly, Thr399Ile, - 1892G/A, and TLR9 Pro545Pro polymorphisms were similar between patients and controls. We found no association under different genetic models. A haplotype analysis of TLR4 showed no association with either RA or SLE. We found no significant differences in the allelic or genotypic frequencies of TLR4 Asp299Gly, Thr399IIe, - 1892G/A, or TLR9 Pro545Pro between patients and controls. These findings suggested that these variants are not risk factors for RA or SLE in Mexican patients.
Toll 样受体(TLR)介导的信号通路诱导促炎微环境以消灭病原体。然而,在类风湿关节炎(RA)和系统性红斑狼疮(SLE)中,TLR 可促进慢性炎症。已经表明,一些 TLR4 和 TLR9 单核苷酸多态性(SNP)是 RA 和 SLE 的危险因素,但这些发现并非在所有人群中均得到复制;因此,结果尚无定论。我们评估了 TLR4 的 Asp299Gly、Thr399Ile、-1892G/A 单核苷酸多态性和 TLR9 的 Pro545Pro 单核苷酸多态性,以评估其与墨西哥患者的 RA 和 SLE 之间的潜在关联。这项研究包括 474 例 RA 患者、283 例 SLE 患者和 424 名健康对照者。我们使用 5' 核酸酶等位基因区分检测法对个体的四个 TLR4 和 TLR9 多态性进行基因分型。我们发现 TLR4 的 Asp299Gly、Thr399Ile、-1892G/A 和 TLR9 的 Pro545Pro 多态性的基因型或等位基因频率在患者和对照组之间相似。我们在不同的遗传模型下未发现关联。TLR4 的单体型分析与 RA 或 SLE 均无关联。我们未发现 TLR4 的 Asp299Gly、Thr399Ile、-1892G/A 或 TLR9 的 Pro545Pro 多态性的等位基因或基因型频率在患者和对照组之间存在显著差异。这些发现表明,这些变体不是墨西哥患者发生 RA 或 SLE 的危险因素。