Zaichko Kateryna, Zaichko Nataliia, Maievskyi Oleksandr, Korotkyi Oleksandr, Falalyeyeva Tetyana, Fagoonee Sharmila, Pellicano Rinaldo, Abenavoli Ludovico, Stanislavchuk Mykola
National Pirogov Memorial Medical University, Vinnytsia, Ukraine.
Institute Biology and Medicine, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
Rev Recent Clin Trials. 2020;15(2):145-151. doi: 10.2174/1574887115666200416143512.
Rheumatoid Arthritis (RA) is an autoimmune polygenic disease characterized by rapid disability progression and high prevalence. Progression of RA is closely associated with chronobiological changes in the production of some hormones and inflammatory mediators, influencing the disease course and therapy efficacy. The main pathogenetic mechanism of RA is angiogenesis, which is controlled by biological clock-genes. Further investigation of circadian rhythms of angiogenic mediators production in RA patients may be considered as important and relevant. The aim of this study was to establish daily variability of serum endothelial Nitric Oxide Synthase (NOS3) and toll-like receptors 2 (sTLR2) levels in female RA patients depending on the NOS3 gene polymorphism.
We examined 173 RA patients (100% female) aged 43.7 ± 7.35 years and 34 age-matched healthy women without joint diseases and autoimmune diseases (control). RA was diagnosed by ACR/EULAR 2010 criteria. Blood serum NOS3 and sTLR2 levels were determined at 08:00 and 20:00 using Cloud-Clone Corp kits (USA). NOS3 T-786С (rs2070744) polymorphism was determined by Real-Time PCR (Bio-Rad iCycler IQ5) using SNP-express kits. The SPSS22 software package was used for statistical processing of the results.
Females with RA demonstrated oppositely directed serum NOS3 and sTLR2 daily changes: NOS3 level in the morning (08:00) was lower than in the evening (+ 45.5 ± 30.7%), and sTLR2 level in the evening (at 20:00) was lower than in the morning (-21.6 ± 13.1%). RA patients had differences in NOS3 and sTLR2 production depending on NOS3 T786C genotype. CC subjects had NOS3 level at 08:00, 20:00 and day average levels lower (16-25%), and sTLR2 level higher (24-27%) than those of TT subjects. RA patients, carriers of CC genotype, had higher chances of NOS3 and sTLR2 aberrant production compared to TT and TC genotype carriers (OR = 2.99 and 4.79, respectively).
RA patients demonstrated oppositely directed circadian changes of serum NOS3 and sTLR2. CC genotype carriers had lower NOS3 and higher sTLR2 production rates than TT and TC genotype carriers.
类风湿关节炎（RA）是一种自身免疫性多基因疾病，其特征为残疾进展迅速且患病率高。RA的进展与某些激素和炎症介质产生的生物钟变化密切相关，影响疾病进程和治疗效果。RA的主要发病机制是血管生成，其受生物钟基因控制。进一步研究RA患者血管生成介质产生的昼夜节律可能被认为是重要且相关的。本研究的目的是根据NOS3基因多态性确定女性RA患者血清内皮型一氧化氮合酶（NOS3）和 Toll样受体2（sTLR2）水平的每日变化。
我们检查了173名年龄在43.7±7.35岁的RA患者（100%为女性）和34名年龄匹配、无关节疾病和自身免疫性疾病的健康女性（对照组）。RA根据2010年ACR/EULAR标准进行诊断。使用美国Cloud-Clone Corp试剂盒在08:00和20:00测定血清NOS3和sTLR2水平。使用SNP-express试剂盒通过实时PCR（Bio-Rad iCycler IQ5）测定NOS3 T-786С（rs2070744）多态性。结果采用SPSS22软件包进行统计处理。
患有RA的女性血清NOS3和sTLR2呈现相反方向的每日变化：早晨（08:00）的NOS3水平低于晚上（升高45.5±30.7%），晚上（20:00）的sTLR2水平低于早晨（降低21.6±13.1%）。RA患者根据NOS3 T786C基因型在NOS3和sTLR2产生方面存在差异。CC基因型受试者在08:00、20:00和日均水平的NOS3水平低于TT基因型受试者（低16 - 25%），而sTLR2水平高于TT基因型受试者（高24 - 27%）。与TT和TC基因型携带者相比，CC基因型的RA患者发生NOS3和sTLR2异常产生的可能性更高（OR分别为2.99和4.79）。
RA患者血清NOS3和sTLR2呈现相反方向的昼夜变化。CC基因型携带者的NOS3产生率低于TT和TC基因型携带者，而sTLR2产生率更高。
