Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease with strong genetic influence, especially upon immune response components. Several cytokines from the toll-like receptors activation pathway display recognized role for RA establishment. However, few studies have verified the role of key mediators such as MYD88 gene and its genetic variants. In the present study, we aim to evaluate the rs6853 functional single-nucleotide variation (SNV) role in RA etiopathogenesis, clinical severity status, and its impact in MYD88 mRNA levels and IL-lβ protein levels. For the association study, a total of 423 RA patients and 346 health individuals, enrolled as control, from Northeast and Southeast Brazil were genotyped using specific Taqman probe. For the gene expression assays, we performed a MYD88 rs6853 genotype-guided monocyte cell culture divided into non-stimulated and lypopolysaccharides (LPS)-stimulated cells from healthy individuals. MYD88 gene expression was measured using primer specifics while IL-1β levels were evaluated by ELISA. We observed that A allele and AA genotype were associated to an increased risk to RA development (OR = 1.60; 95% CI 1.24–2.08; p = 0.0004/OR = 2.83; 95% CI 1.25–6.41; p = 0.0152). The AA genotype exhibited lower MYD88 mRNA levels than GG genotype in non-stimulated monocyte cell culture (FC − 3.83; p = 0.003). Additionally, we verified an increase of IL-1β levels when AA genotype non-stimulated monocytes were compared to AA genotype LPS-stimulates (p = 0.021). In summary, MYD88 rs6853 polymorphism associated to RA development in our Brazilian cohort and showed influence upon MYD88 mRNA levels’ expression and IL-lβ production.

类风湿性关节炎 (RA) 是一种自身免疫性和炎症性疾病，具有很强的遗传影响，尤其是对免疫反应成分的影响。来自 toll 样受体激活途径的几种细胞因子显示出公认的 RA 建立作用。然而，很少有研究验证关键介质如MYD88基因及其遗传变异的作用。在本研究中，我们旨在评估 rs6853 功能性单核苷酸变异 (SNV) 在 RA 发病机制、临床严重程度状态及其对MYD88 的影响中的作用mRNA水平和IL-1β蛋白水平。对于关联研究，使用特定的 Taqman 探针对来自巴西东北部和东南部的总共 423 名 RA 患者和 346 名健康个体（作为对照）进行了基因分型。对于基因表达测定，我们进行了MYD88 rs6853 基因型引导的单核细胞培养，将健康个体的细胞分为非刺激细胞和脂多糖 (LPS) 刺激细胞。使用引物特异性测量MYD88基因表达，而通过 ELISA 评估 IL-1β 水平。我们观察到 A 等位基因和 AA 基因型与 RA 发展的风险增加有关（OR = 1.60；95% CI 1.24–2.08；p  = 0.0004/OR = 2.83；95% CI 1.25–6.41；p  = 0.0152）。AA 基因型表现出较低的MYD88 mRNA 水平高于非刺激单核细胞培养物中的 GG 基因型（FC - 3.83；p  = 0.003）。此外，当 AA 基因型非刺激单核细胞与 AA 基因型 LPS 刺激相比时，我们证实了 IL-1β 水平的增加（p  = 0.021）。总之，MYD88 rs6853 多态性与我们巴西队列中的 RA 发展相关，并显示出对MYD88 mRNA 水平的表达和 IL-1β 产生的影响。