Paradowska-Gorycka Agnieszka, Sowinska Anna, Pawlik Andrzej, Malinowski Damian, Stypinska Barbara, Haladyj Ewa, Romanowska-Prochnicka Katarzyna, Olesinska Marzena
Department of Biochemistry and Molecular Biology, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.
Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznan, Poland.
PLoS One. 2017 Mar 21;12(3):e0172018. doi: 10.1371/journal.pone.0172018. eCollection 2017.
Inflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the FLT-1 polymorphisms with different "angiogenic diseases" suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify FLT-1 genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA.
The FLT-1 gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated.
The FLT-1 gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the FLT-1 rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D' = 0.97 and r2 = 0.83. The FLT-1 rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, FLT-1 genetic variants conferred higher sFLT-1 levels in RA patients compared to controls.
FLT-1 rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA.
炎症和血管生成是类风湿关节炎（RA）发病机制的重要因素。促炎细胞因子产生的触发因子FLT-1可能与RA患者的炎症有关。FLT-1基因多态性与不同“血管生成性疾病”的关联表明，它可能也是RA的一个新的遗传危险因素。本研究的目的是鉴定FLT-1基因变异及其与可溶性FLT-1（sFLT-1）水平、RA易感性和严重程度的可能关联。
对471例RA患者和684名健康个体进行FLT-1基因多态性基因分型。对临床参数、心血管疾病（CVD）和抗瓜氨酸化肽/蛋白抗体（ACPA）的存在情况进行相关性分析。评估sFLT-1血清水平。
FLT-1基因多态性在病例组和对照组中的比例无显著差异。此外，FLT-1 rs2296188 T/C多态性与ACPA阳性的RA相关。总体而言，rs9943922 T/C和rs2296283 G/A几乎完全处于连锁不平衡（LD）状态，D' = 0.97，r2 = 0.83。FLT-1 rs7324510 A等位基因与视觉模拟评分（VAS）（p = 0.035）、疾病活动评分28（DAS-28）（p = 0.013）和早期类风湿关节炎（ExRA）的存在（p = 0.027）相关。此外，具有该等位基因的RA患者的其他临床参数也更高。此外，与对照组相比，FLT-1基因变异使RA患者的sFLT-1水平更高。
FLT-1 rs7324510 C/A变异可能是RA严重程度的一个新的遗传危险因素。所检测的因素使RA更易出现更严重的疾病活动以及更高的sFLT-1水平。
