Ficolin-1 and ficolin-3 polymorphisms and susceptibility to rheumatoid arthritis.

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.