سنجش بيان ژن‌هاي مرتبط با بيماري آرتريت روماتوئيد (RA)

Rheumatoid arthritis (RA) is a chronic inflammatory disorder in which a personʹs immune system attacks the lining of joints throughout the body. Clinically, the symptoms of RA vary between the early an‎d late stages of the disease. If RA is not treated, a complex clinical picture develops with the occurrence of serious systemic symptoms an‎d ultimately leads to increased mortality. The exact cause of RA is not fully understood, but it is believed to be the result of complex interactions between genetic an‎d non-genetic factors. RA is a multifactorial disease that is caused by an inappropriate response to environmental challenges in a genetically predisposed person. Many researches show that psychological stress an‎d its interactions with the immune system through the production of pro-inflammatory cytokines play a fundamental role in the etiology of RA; These cytokines are the main triggers of joint inflammation in RA. In addition to inflammatory effects, long-term psychological stress impairs antioxidant defense in RA. Inflammation an‎d oxidative stress in RA reinforce each other; Therefore, a vicious cycle is observed in RA disease. Coenzyme A biosynthesis pathway plays an important role in maintaining redox balance an‎d managing oxidative stress in cells an‎d is the chosen pathway in this research. Untreated individuals in the early stages of RA have distinct gene expression profiles that reflect pathogenic mechanisms in disease initiation an‎d progression; Therefore, early diagnostic biomarkers are essential for timely treatment. Peripheral blood, with easy access an‎d minimal invasiveness, shows a good reflection of transcriptional changes related to inflammation an‎d oxidative stress. This research was conducted to investigate the expression of the gene related to CoA biosynthesis in the peripheral blood of untreated RA patients with a history of mental stress, as a biomarker (diagnostic blood), in the early stages of the disease, so that if there are significant expression changes in the blood of the patients, In the future, it will be introduced for early detection kit through blood test. In this meta-analysis study, microarray an‎d RNA-sequencing data related to early RA patients without receiving medication in the GEO database were reviewed with DEG an‎d WGCNA studies. The VNN1 gene, which plays a vital role in the CoA biosynthesis pathway an‎d is known as an oxidative stress sensor in peripheral blood mononuclear cells, was selec‎ted an‎d its expression was determined by real-time PCR in peripheral blood mononuclear cells of 45 patients with RA. Initially, without receiving medication an‎d a history of mental stress, it was measured in comparison with 30 healthy control subjects. The results of the data obtained by the relative expression analysis method an‎d t-test showed that the expression level of the VNN1 gene in the blood of RA patients showed a significant decrease compared to healthy individuals. In this study, the ROC curve was used to examine the specificity an‎d sensitivity of this gene. The results of the ROC test showed that the VNN1 gene can separate the patient population from the healthy population with high discrimination power. Therefore, it is suggested that the expression pattern of the VNN1 gene can be used as a biomarker related to the CoA biosynthesis pathway an‎d also as a sensor of oxidative stress in peripheral blood mononuclear cells of untreated RA patients with a history of psychological stress for the early diagnosis of this disease.

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