Department of Genetic Diagnostics, State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine.
State Institution «Reference-centre for Molecular Diagnostic of Public Health Ministry of Ukraine», Kyiv, Ukraine.
Nitric Oxide. 2023 May 1;134-135:44-48. doi: 10.1016/j.niox.2023.04.002. Epub 2023 Apr 8.
There is a hypothesis that a sufficient level of endothelial nitric oxide synthase is important for reliable protection against COVID-19. Theoretical ideas about the NOS3 gene demonstrated that it can have an effect on links of the complications pathogenesis in COVID-associated pneumonia. We determined the goal - to investigate the association of the NOS3 gene variants with the occurrence of the disease and its clinical course in patients of the intensive care unit.
The study group included 117 patients with a diagnosis of severe "viral COVID-19 pneumonia". Determination of NOS3 gene variants was performed using the PCR method. The probability of differences in the quantitative results were determined using ANOVA or Kruskal-Wallis test (depend of normality of studied parameters).
Our results indicate that the presence of the NOS3 gene 4a allele increase the risk of complicated COVID-19-associated pneumonia (χ = 18.84, p = 0.00001, OR = 3.53 (1.95-6.39)). It was showed, that carriers of the 4aa genotype had a significantly higher ratio of SpO/FiO on the first and second days after hospitalization (p = 0.017 and p = 0.03, respectively). Patients with the 4aa genotype also had the acid-base imbalances, as showed by indicators of base deficiency and standard bicarbonate, which were beyond the reference values. Potassium and sodium concentrations on the first and second day after hospitalization were also significantly lower in patients with 4aa genotype (p = 0.009 and p = 0.048, respectively), for whom, in the same time, the concentrations of C-reactive protein and total bilirubin were significantly higher (p = 0.002 and p = 0.033, respectively).
Our results confirmed that the rs61722009 variant of the NOS3 gene is associated with an increased risk of severe СOVID-19-associated pneumonia and its adverse clinical course with potential progression of kidney and liver damage, and occurrence risk of systemic inflammatory response syndrome. These results require further research for the new metabolic strategy formation, in order to prevent the severe COVID-19 associated pneumonia and its complications.
有一种假说认为,内皮型一氧化氮合酶的水平足够高对于可靠地预防 COVID-19 是重要的。关于 NOS3 基因的理论观点表明,它可能对 COVID 相关肺炎并发症发病机制的环节产生影响。我们确定了目标-研究 NOS3 基因变异与重症监护病房患者疾病发生及其临床过程的相关性。
研究组包括 117 名被诊断为严重“病毒性 COVID-19 肺炎”的患者。使用 PCR 法测定 NOS3 基因变异。使用方差分析或克鲁斯卡尔-沃利斯检验(取决于研究参数的正态性)确定定量结果差异的概率。
我们的结果表明,NOS3 基因 4a 等位基因的存在增加了合并 COVID-19 相关肺炎的风险(χ=18.84,p=0.00001,OR=3.53(1.95-6.39))。结果表明,住院后第 1 天和第 2 天,4aa 基因型携带者的 SpO/FiO 比值显著更高(p=0.017 和 p=0.03)。4aa 基因型患者的酸碱失衡指标,如碱缺乏和标准碳酸氢盐,也超出了参考值。住院后第 1 天和第 2 天,4aa 基因型患者的钾和钠浓度也显著更低(p=0.009 和 p=0.048),同时,他们的 C 反应蛋白和总胆红素浓度也显著更高(p=0.002 和 p=0.033)。
我们的结果证实,NOS3 基因的 rs61722009 变异与严重 COVID-19 相关肺炎及其不良临床过程相关,包括潜在的肾和肝损伤进展以及全身炎症反应综合征的发生风险。这些结果需要进一步研究以制定新的代谢策略,以预防严重的 COVID-19 相关肺炎及其并发症。