Variants of nucleotide sequences in vascular remodeling and renin-angiotensin-aldosterone system genes in patients with coronary artery disease in the post-covid period

Introduction. Despite the official end of the COVID-19 pandemic, its long-term consequences continue to significantly impact patients with cardiovascular disease. Particular attention should be paid to individuals with coronary artery disease (CAD).
Aim. To compare nucleotide sequence variants of RAAS and vascular endothelial regulation genes in CAD patients with prior COVID-19 infection (>12 weeks post-infection), stratified by CAD onset timing.
Materials and methods. The study enrolled 431 patients with stable CAD and confirmed COVID-19 (>12 weeks prior). The cohort was divided into: Group 1 – new-onset CAD post-COVID; Group 2 – pre-existing CAD before COVID-19. Real-time allele-specific PCR genotyped 11 key polymorphic loci in RAAS and endothelial regulation genes, followed by χ² and multivariate logistic regression analysis.
Results. The frequency of hemodynamically significant coronary artery stenosis in patients with pre-existing coronary artery disease (CAD) before COVID-19 has been found to be significantly higher than in patients with de novo CAD in the post-COVID period. The patients showed no significant between-group differences in the frequency of nucleotide sequence variants of genes AGT (rs4762), AGTR1 (rs5186), ACE (rs1799752), AGT (rs699), GNB3 (rs5443), CYP11B2 (rs1799998), EDN (rs 5370). However, significant differences were identified in the frequencies of heterozygous genotypes of the eNOS (rs2070744) and ADD1 (rs4961) gene, which were more common in patients with de novo CAD in the post-COVID period. In contrast, homozygous genotypes of the eNOS (-786 TT) gene, ADD1 (1378 GG) gene, and eNOS (894 GG) gene, as well as the heterozygous genotype of the IL-10 gene (1082 AG), prevailed in group 2 patients.
Conclusions. These findings enable genetic risk stratification for post-COVID cardiovascular complications. The association between eNOS polymorphisms and new-onset CAD highlights potential targets for personalized endothelial dysfunction therapy.

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