Association between renin-angiotensin system gene polymorphism and cardio-ankle vascular index in patients with COVID-19

Aim . To assess the relationship between arterial stiffness and renin-angiotensin system (RAS) gene polymorphism in patients with COronaVIrus Disease 2019 (COVID-19). Material and methods : 100 patients (mean age of 58.1±11.98 years; 51% women, 49% men) were included in the cross-ectional study. This study included adult patients with laboratory-confirmed diagnosis of COVID-19 admitted to the University Hospital. All patients were evaluated for arterial stiffness using cardio-ankle vascular index (CAVI) by sphygmomanometry. Also alleles and genotypes of several polymorphic markers were identified by real-time polymerase chain reaction in human DNA preparations: rs4762 of angiotensinogen (AGT) gene, rs1799752 of angiotensin-converting enzyme type 1 gene (ACE1), rs5186 of angiotensin II type 1 receptor gene (ATP1), and rs1403543 of angiotensin II type 2 receptor gene (ATP2). The distributions of alleles and genotypes in groups with normal and elevated arterial stiffness (CAVI ≥9.5) were compared. Results . Elevated arterial stiffness (CAVI ≥9.5) was found in 29%. A significantly higher frequency of ATP1 rs5186 genotypes including the A allele, i.e., A/A + A/C versus C/C , was found in subjects with normal CAVI: 95.0% and 5.0% compared with 87.5% and 12.5% in those with CAVI ≥9.5 (χ2=3.907, p=0.049). A significantly higher frequency of genotypes involving the D allele ( DD and ID ) was detected in patients with increased stiffness: 95.0% compared to 81.3% in the group with normal stiffness (χ2=9.280, p<0.003), and a significantly higher frequency of genotypes including the A -allele: 68.7% and 31.3% compared to 55.0% and 45.0% in individuals with normal arterial stiffness (χ2=4.160, p=0.042). As a result, in patients hospitalized with COVID-19, the presence of increased arterial stiffness with a CAVI level ≥9.5 was associated with a higher frequency of adverse D/D genotype of ACE1 rs1799752 , C/C genotype of ATP1 rs5186 , A/A genotype and A allele of ATP2 rs1403543 . Conclusion . Thus, the presence of certain unfavorable genotypes of ACE1, ATP1 and ATP2 may contribute to the formation of higher arterial stiffness in COVID-19 and be considered as a non-modifiable risk factor for increased vascular wall stiffness along with such a significant factor as age.