МЕХАНІСТИЧНІ АСПЕКТИ ТКАНИННОСПЕЦИФІЧНОЇ РЕГУЛЯЦІЇ ГЕНА NOS3 (RS2070744) ПРИ COVID-19

To investigate the tissue-specific transcriptional effects of the NOS3 promoter variant rs2070744 through eQTL analysis to elucidate its potential regulatory role in endothelial function and its contribution to COVID-19 pathophysiology.Material and methods. Genotyping of the NOS3 gene (rs2070744) locus was performed in 72 patients with moderate-to-severe COVID-19 and 48 patients with a mild course of the disease. Genomic DNA was extracted from peripheral blood leukocytes, and allelic discrimination of the target SNP was conducted using RT-PCR. Tissue-specific transcriptional effects of the NOS3 gene (rs2070744) variant were subsequently eQTL analysis based on publicly available data from the QTLbase database.Results. A total of 82 eQTLs were detected, all of which represented cis-acting regulatory variants spanning thirteen tissues and organs. The NOS3 rs2070744 variant demonstrated transcriptional interactions with 27 genes, with regulatory effects largely driven by the T allele. This allele was primarily linked to reduced expression of several genes, including KCNH2 in the cerebellum and central nervous system, AOC1 in the left ventricular myocardium, WDR86 in induced pluripotent stem cells (iPSCs), and ASB10 in renal tissue. In contrast, the T allele also exhibited transcription-enhancing effects, promoting increased expression of AOC1, ASIC3, GIMAP2, and TMEM176A in adipose tissue, as well as CHPF2 and TMUB1 in iPSCs, dendritic cells, and the kidney.Conclusions. The NOS3 rs2070744 polymorphism exhibits pronounced tissue-specific regulatory activity, with the functional T allele influencing the expression of a broad range of genes. Collectively, these transcriptional effects suggest that this variant may act as a modifier of endothelial and immune function, potentially shaping COVID-19 severity and progression.