ABSTRACT

The complement system is a key component of the innate immunity that plays a significant role in the development and clinical presentation of Rheumatoid arthritis (RA). Complement protein C3 is a central molecule in the activation of complement with a significant role in the inflammatory processes of RA. Nevertheless, the impact of C3 gene polymorphisms in the development of RA is still unknown. The current study aimed to investigate the possible influence of C3 gene polymorphisms in the susceptibility and clinical expression of RA. Three C3 polymorphisms (rs2250656:A > G, intron 2; rs2230199:C > G [p.Arg102Gly], exon 3 and rs1047286:C > T [p.Pro314Leu], exon 9) were assessed by sequence-specific PCR in a total of 156 RA patients and 270 healthy controls from Southern Brazil. In addition, C3 levels were measured in 60 patients and 60 controls by immunoturbidimetry and clinical features were collected from medical records. The frequency of rs2230199 G allele and GG genotype was significantly higher in RA patients than controls (p_adj = 0.012 OR = 1.57 [1.11–2.31]; p_adj = 0.008, OR = 1.60 [1.35–2.33]) as well as the rs1047286 T and TT (p_adj = 0.010, OR = 1.67 [1.12–2.40]; p_adj = 0.001, OR = 1.83 [1.27–2.65] and the C3 AGT haplotype (p_adj = 0.0007 OR = 1.92 [1.32–2.80]). Moreover, C3 serum levels were higher in patients than controls (median: 169 mg/dl vs.155 mg/dl; p_adj = 0.022), as well as in RF seronegative compared with seropositive patients (172 mg/dl vs. 165 mg/dl; p_adj = 0.007). Our results suggest that the rs2230199 G (p.102Gly) and rs1047286 T (p.314Leu) alleles play a role in the pathophysiology of RA, possibly impacting complement activation by the alternative pathway.

摘要

补体系统是先天免疫的关键组成部分，在类风湿性关节炎 (RA) 的发展和临床表现中起着重要作用。补体蛋白 C3 是补体激活的中心分子，在 RA 的炎症过程中具有重要作用。然而，C3基因多态性对RA发展的影响仍然未知。本研究旨在探讨C3基因多态性对RA易感性和临床表达的可能影响。通过序列特异性 PCR 在 a来自巴西南部的总共 156 名 RA 患者和 270 名健康对照者。此外，通过免疫比浊法测量 60 名患者和 60 名对照者的 C3 水平，并从医疗记录中收集临床特征。rs2230199的频率RA 患者的G等位基因和 GG 基因型显着高于对照组（p _adj  = 0.012 OR = 1.57 [1.11-2.31]；p _adj  = 0.008，OR = 1.60 [1.35-2.33]）以及 rs1047286 T和 TT（ p _adj  = 0.010, OR = 1.67 [1.12–2.40]; p _adj  = 0.001, OR = 1.83 [1.27–2.65] 和 C3 AGT单倍型 (p _adj  = 0.0007 OR = 1.92 [1.32–2.80])。此外，C3患者的血清水平高于对照组（中位数：169 mg/dl 对 155 mg/dl；p _adj  = 0.022），与血清阳性患者相比，RF 血清阴性患者（172 mg/dl 对 165 mg/dl； p _adj  = 0.007). 我们的结果表明 rs2230199 G(p.102Gly) 和 rs1047286 T (p.314Leu) 等位基因在 RA 的病理生理学中起作用，可能通过替代途径影响补体激活。