Abstract

Rheumatoid arthritis (RA) is an autoimmune disease, which compromises the synovial membrane resulting in chronic inflammation. Ficolins are key proteins of the lectin pathway of complement able to recognize pathogen-associated molecular patterns, apoptotic cells, and cellular debris mediating the clearance by phagocytes. High ficolin-1 and ficolin-3 levels have been observed in RA patients, however, the influence of polymorphisms in the FCN1 gene in RA is not completely established, while no study evaluated FCN3 gene polymorphisms in RA to date. We investigated the influence of FCN1 and FCN3 gene polymorphisms in the susceptibility and clinical presentation of RA. A total of 148 patients with RA and up to 160 controls from Southern Brazil were genotyped by sequence-specific PCR (PCR-SSP) for five FCN1 promoter polymorphisms (rs2989727, rs10120023, rs17039495, rs10117466, and rs10858293) and three FCN3 gene variants (rs532781899, rs28362807, and rs4494157). The FCN1 g.-542GG (rs10120023) genotype and g.-542G allele, were associated with increased susceptibility to RA (p = .025, OR = 1.69 [1.07–2.69]; p = .041, OR = 1.47 [1.02–2.12], respectively) and related to decreased FCN1 gene expression in whole blood (p < .00001), according to gene expression databases. In addition, the FCN1 AAGAG haplotype was more prevalent in rheumatoid factor seronegative in comparison to seropositive patients (p = .006, OR = 0.042 [0.002–0.80]). There was no association of FCN3 polymorphisms with the susceptibility or clinical characteristics of RA. Our results indicate that the FCN1 rs10120023 [g.-542G>A] polymorphism in the promoter region might contribute to RA susceptibility, probably by impacting FCN1 gene expression.

 抽象的

类风湿性关节炎 (RA) 是一种自身免疫性疾病，会损害滑膜，导致慢性炎症。 Ficolins 是补体凝集素途径的关键蛋白，能够识别病原体相关分子模式、凋亡细胞和介导吞噬细胞清除的细胞碎片。在 RA 患者中观察到高 ficolin-1 和 ficolin-3 水平，然而， FCN1基因多态性对 RA 的影响尚未完全确定，迄今为止还没有研究评估 RA 中FCN3基因多态性的影响。我们研究了FCN1和FCN3基因多态性对 RA 易感性和临床表现的影响。通过序列特异性 PCR (PCR-SSP) 对来自巴西南部的总共 148 名 RA 患者和多达 160 名对照进行了基因分型，检测了 5 个FCN1启动子多态性（rs2989727、rs10120023、rs17039495、rs10117466 和 rs10858293）和 3 个FCN3基因变异（ rs532781899、rs28362807 和 rs4494157）。 FCN1 g.-542GG (rs10120023) 基因型和g.-542G等位基因与 RA 易感性增加相关（ p = .025，OR = 1.69 [1.07–2.69]； p = .041，OR = 1.47 [1.02–根据基因表达数据库，分别为 2.12]，并且与全血中FCN1基因表达降低有关 ( p < .00001)。此外，与血清阳性患者相比， FCN1 AAGAG单倍型在类风湿因子血清阴性患者中更为常见（ p = .006，OR = 0.042 [0.002–0.80]）。 FCN3多态性与 RA 的易感性或临床特征没有关联。 我们的结果表明，启动子区域的FCN1 rs10120023 [g.-542G>A] 多态性可能通过影响FCN1基因表达而导致 RA 易感性。