Allele С (rs5186) of at1r is associated with the severity of COVID-19 in the Ukrainian population

Abstract

Introduction The severity of SARS-CoV-2 induced coronavirus disease 19 (COVID-19) depends on the presence of risk factors and the hosts' gene variability. There are preliminary results that gene polymorphisms of the renin-angiotensin system can influence the susceptibility to and mortality from COVID-19. Angiotensin II type 1 receptor (AT1R) might be a gene candidate that exerts such influence. The aim of this study was to elaborate on the association between A1166C at1r polymorphic variants and the susceptibility to and severity of COVID-19 in the Ukrainian population. Methods The study population consisted of the Ukrainian population (Poltava region) with COVID-19, divided into three clinical groups in accordance with oxygen requirement: patients without oxygen therapy ( n = 110), with non-invasive ( n = 136) and invasive ( n = 36) oxygen therapy. The A1166C polymorphism of the at1r was determined by polymerase chain reaction with subsequent restrictase analysis. In an attempt to better explain the role of the A1166C at1r polymorphism we compared its association with COVID-19, essential hypertension ( n = 79), renoparenchimal hypertension ( n = 30) and dyscirculatory encephalopathy ( n = 112). The data for this comparison were obtained by meta-analysis. Results We observed significant differences in the frequency of AA, AC and CC genotypes in the groups of COVID-19 patients with non-invasive and invasive oxygen therapy in comparison with control subjects as well as in the frequency of combined AC + CC genotype between the groups of COVID-19 patients with any types of oxygen therapy and patients without oxygen therapy. The frequency of the 1166C allele was higher in COVID-19 patients with invasive oxygen therapy (OR = 2.06; CI (1.20–3.53); p = 0.013). We obtained important results indicating that there were no differences between the frequency of at1r polymorphisms in patients with cardiovascular disease and severe COVID-19 with invasive oxygen therapy as well as those who died due to COVID-19. Conclusion Our study indicated the presence of an association between the A1166C at1r polymorphisms and the severity of COVID-19 in the Ukrainian population. It seems that in carriers of 1166C at1r , the severity of COVID-19 and oxygen dependency is higher as compared to the A allele carriers, possibly, due to cardiovascular disorders.

A protective erythropoietin evolutionary landscape, NLRP3 inflammasome regulation, and multisystem inflammatory syndrome in children

“…As RAAS activity is an important regulator of eNOS activity, genetic polymorphisms for molecules in the RAAS signaling axis (Table 2 ) are likely to have significant impact on NO generation, NLRP3 regulation, and endothelial inflammation during MIS-C (Fig. 2 ) [ 15 , 21 , 56 – 62 , 103 , 104 ]. Polymorphisms of the ACE gene explain 20–50% of the variability in ACE levels and up to 15% of hypertensive cases [ 105 ].…”

“…Given the fundamental role of RAAS in cardiovascular homeostasis and SARS-CoV-2, RAAS molecule polymorphisms could significantly modulate Ang II activity and increase the risk of a RAAS-induced hyperinflammation with excessive NLRP3 inflammasome activation, when increasing age and co-inherited eNOS activity-reducing NOS3 haplotypes, attenuate EPO effects (Fig. 1 , 2 ) [ 15 , 21 , 22 , 30 , 56 – 62 , 104 , 106 – 110 ].…”

Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

“…More than 700 mutations, that can overactivate or inactivate the receptors, have been identified and linked to more than 30 distinct human illnesses [ 15 ]. Minor information about AT1R polymorphisms in SARS-CoV-2 patients is found, despite their importance as risk factors in COVID-19 such as those implicated in diabetes, hypertension, and cardiovascular diseases (CVDs) [ 28 ].…”

“…The study of Izmailova et al on the Ukrainian population showed an association between COVID-19 severity and the A1166C polymorphism. When compared with A-allele carriers, C allele carriers had significant COVID-19 pathogenicity, as well as higher oxygen requirement due to cardiovascular problems [ 28 ]. In fact, the C allele has been shown to be associated with many CVDs such as systolic blood pressure, left ventricular hypertrophy, hypertension, aortic stiffness, myocardial infarction, carotid intimal–medial thickening, coronary artery disease, and stroke [ 32 , 33 ].…”

High-Altitude Pulmonary Edema in the Context of COVID-19

“…Prolyl hydroxylase domain protein 2 (EGLN1) and HIF-1α inhibitory factor (HIF1AN) are also associated with the pathophysiology of HAPE [8], and abnormally elevated levels of HIF-1α are considered to be a HAPE susceptibility marker [9]. Additionally, angiotensin II type 1 receptor (AT1R) gene polymorphisms might be associated with HAPE susceptibility [10], and A1166C AT1R polymorphism is also associated with COVID-19 severity [11]. Interestingly, a slightly elevated plasma concentration of B-type natriuretic peptide might be related to an exaggerated pulmonary vascular response in hypoxia-susceptible individuals [12], as well as poor outcomes in COVID-19 patients [13].…”