Laboratory of Molecular Immunopathology, Clinical Hospital, Federal University of Paraná, Curitiba, Brazil.
Rheumatology Unit, Evangelical Mackenzie Hospital, Curitiba, Brazil.
Autoimmunity. 2020 Nov;53(7):400-407. doi: 10.1080/08916934.2020.1809654. Epub 2020 Aug 21.
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 gene in RA is not completely established, while no study evaluated gene polymorphisms in RA to date. We investigated the influence of and 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 promoter polymorphisms (rs2989727, rs10120023, rs17039495, rs10117466, and rs10858293) and three gene variants (rs532781899, rs28362807, and rs4494157). The g.-542GG (rs10120023) genotype and allele, were associated with increased susceptibility to RA ( = .025, OR = 1.69 [1.07-2.69]; = .041, OR = 1.47 [1.02-2.12], respectively) and related to decreased gene expression in whole blood ( < .00001), according to gene expression databases. In addition, the haplotype was more prevalent in rheumatoid factor seronegative in comparison to seropositive patients ( = .006, OR = 0.042 [0.002-0.80]). There was no association of polymorphisms with the susceptibility or clinical characteristics of RA. Our results indicate that the rs10120023 [g.-542G>A] polymorphism in the promoter region might contribute to RA susceptibility, probably by impacting gene expression.
类风湿关节炎（RA）是一种自身免疫性疾病，会损害滑膜，导致慢性炎症。纤维胶凝蛋白是补体凝集素途径的关键蛋白，能够识别病原体相关的分子模式、凋亡细胞和细胞碎片，从而介导吞噬细胞的清除。已经观察到 RA 患者的纤维胶凝蛋白-1 和纤维胶凝蛋白-3 水平升高，然而，基因多态性在 RA 中的影响尚未完全确定，目前尚无研究评估 RA 中基因多态性。我们研究了基因和基因多态性对 RA 易感性和临床表现的影响。总共招募了来自巴西南部的 148 名 RA 患者和多达 160 名对照，通过序列特异性聚合酶链反应（PCR-SSP）对 5 个启动子多态性（rs2989727、rs10120023、rs17039495、rs10117466 和 rs10858293）和 3 个基因变异（rs532781899、rs28362807 和 rs4494157）进行了基因分型。-542GG（rs10120023）基因型和等位基因与 RA 的易感性增加相关（=0.025，OR=1.69[1.07-2.69]；=0.041，OR=1.47[1.02-2.12]），并且与全血中基因表达降低相关（<.00001），根据基因表达数据库。此外，与类风湿因子阳性患者相比，该单倍型在类风湿因子阴性患者中更为常见（=0.006，OR=0.042[0.002-0.80]）。基因多态性与 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 rs10120023[g.-542G>A]多态性可能导致 RA 易感性增加，可能是通过影响基因表达。
