Alenzi Faris Q
College of Appl. Med. Sci, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
Saudi J Biol Sci. 2016 Nov;23(6):767-772. doi: 10.1016/j.sjbs.2016.04.015. Epub 2016 May 4.
On the basis that the inflammatory effects of TNF (tumour necrosis factor) are predominantly mediated through interaction with the TNF receptor-1 (TNFRSF1A), the current study was designed to establish the prevalence of the mutations, R92Q and P46L TNFRSF1A polymorphisms both in the general healthy Saudi population, and in Saudi patients carrying inflammatory diseases such as atherosclerosis or rheumatoid arthritis. We felt it important to report the frequency of the mutations, R92Q and P46L TNFRSF1A polymorphisms in healthy Saudi individuals, and those with inflammatory conditions, as well as to describe the pattern of immunological factors in individuals expressing R92Q or P46L TNFRSF1A. We collected in PAX gene blood RNA tubes (for RT-PCR and sequencing) 500 blood samples from normal healthy individuals from the West and Center of Saudi Arabia, as well as 100 from patients with atherosclerosis, and 100 patients diagnosed with rheumatoid arthritis. All were screened for the levels of soluble TNF, C-reactive protein (CRP), interleukin6 (IL-6) and sTNFR1. In addition, they were screened for R92Q and P46L TNFRSF1A by RT-PCR. Moreover, phenotype and expression of peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry (FACS). Across 500 normal individuals, 8 (1.6%) expressed both R92Q and P46L mutations. By contrast, of the 100 patients in our study with atherosclerosis, 34% expressed both the R92Q and P46L mutations, whilst 42% of patients with rheumatoid arthritis expressed both mutations R92Q and P46L. No significant differences were observed between cell markers of normal individuals (CD3, 4, 8, 16, 56, 19, 25, ICAM-1, VLA-4 & l-selectin) and patients with atherosclerosis. There were significantly high values of cell markers in patients with rheumatoid arthritis compared with normal individuals both in terms of percentage and absolute counts ( < 0.05). Soluble IL-6 and sTNFR1 showed significant decreases in atherosclerosis and rheumatoid arthritis when compared with controls ( < 0.05). In addition, CRP and sTNF showed significant increases in the atherosclerosis and rheumatoid arthritis groups when compared to controls ( < 0.05). Our findings reasonably anticipate the presence of TRAPS disease (low penetrance mutations) amongst the Saudi population although further studies are needed to confirm these results.
基于肿瘤坏死因子（TNF）的炎症效应主要通过与TNF受体-1（TNFRSF1A）相互作用介导，本研究旨在确定R92Q和P46L TNFRSF1A多态性突变在沙特健康人群以及患有动脉粥样硬化或类风湿性关节炎等炎症性疾病的沙特患者中的流行情况。我们认为报告健康沙特个体以及患有炎症性疾病个体中R92Q和P46L TNFRSF1A多态性突变的频率，并描述表达R92Q或P46L TNFRSF1A个体的免疫因子模式非常重要。我们从沙特阿拉伯西部和中部的正常健康个体中收集了500份血液样本，以及100份动脉粥样硬化患者和100份诊断为类风湿性关节炎患者的血液样本，置于PAX基因血液RNA管中（用于逆转录聚合酶链反应和测序）。所有样本均检测了可溶性TNF、C反应蛋白（CRP）、白细胞介素6（IL-6）和可溶性TNF受体1（sTNFR1）的水平。此外，通过逆转录聚合酶链反应对R92Q和P46L TNFRSF1A进行检测。此外，通过流式细胞术（荧光激活细胞分选术）检测外周血单个核细胞（PBMC）的表型和表达。在500名正常个体中，8人（1.6%）同时表达R92Q和P46L突变。相比之下，在我们研究的100名动脉粥样硬化患者中，34%同时表达R92Q和P46L突变，而42%的类风湿性关节炎患者同时表达R92Q和P46L突变。正常个体（CD3、4、8、16、56、19、25、细胞间黏附分子-1、极晚期抗原-4和淋巴细胞选择素）和动脉粥样硬化患者的细胞标志物之间未观察到显著差异。与正常个体相比，类风湿性关节炎患者的细胞标志物在百分比和绝对计数方面均显著升高（P<0.05）。与对照组相比，可溶性IL-6和sTNFR1在动脉粥样硬化和类风湿性关节炎患者中显著降低（P<0.
