Polimorfismos de nucleotídeo único dos genes de apolipoproteína A-I (rs670) e B (rs693): associação com lipoproteínas séricas e ativação endotelial em pacientes ambulatoriais com Covid-19

Abstract

Covid-19 causes inflammatory dysregulation, coagulation disorders, endothelial activation and complications in various organs. Dyslipidemias are one of the main risk factors for atherosclerosis and cardiovascular events, in which Covid-19 can be an aggravating factor. Considering the influence of genetic factors, single-nucleotide polymorphisms (SNPs) that occur in the apolipoprotein (Apo) genes are frequently associated with polygenic dyslipidemias, with the SNPs rs670 C>T (Apo A-I) and rs693 G>A (Apo B) being the most investigated. This observational, analytical and cross-sectional study investigated the association of SNPs rs670 and rs693 with parameters of lipid metabolism and endothelial activation in 86 Covid-19 outpatients, matched for sex and age with 81 healthy individuals. Serum levels of total

cholesterol (TC) and fractions and triglycerides (TG) were determined using an enzymatic- colorimetric method, Apo A-I and B by immunoturbidimetric method and vascular cell

adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay (ELISA). Genotyping of SNPs rs670 and rs693 was carried out using fluorescent TaqManTM hydrolysis probes (VIC - green and FAM - blue) in quantitative polymerase chain reaction (qPCR) using leucocyte genomic DNA (gDNA) samples extracted from whole blood. A p-value < 0.05 was adopted. Covid-19 outpatients were associated with an increase in total cholesterol (TC) (187.0 ± 48.3 vs. 160.8 ± 32.0; p < 0.001), low-density lipoprotein cholesterol (LDL-c) (110.3 ± 41.5 vs. 98.8 ± 28.2; p = 0.036), non-high-density lipoprotein cholesterol (non-HDL-c) (138.3 ± 45.8 vs. 115.6 ± 31.6; p < 0.001), TG (139.7 ± 80.3 vs. 84.9 ± 35.1; p < 0.001), and Apo A-I (149.5 ± 40.0 vs. 133.3 ± 20.9; p = 0.001), as well as a higher frequency of hypercholesterolemia and hypertriglyceridemia. VCAM-1 levels were, on average, double those of the control (682.7 ± 231.8 vs. 299.3 ± 102.9; p < 0.001), and showed high predictive power for Covid-19 (area under the curve = 0.946; p < 0.001). Furthermore, VCAM-1 correlated negatively with TC (r = -0.223; p = 0.039) and HDL-c (r = -0.225; p = 0.037). The dominance of the T polymorphic allele and the codominance of the T and A polymorphic alleles were predictors of reduced TG and VCAM-1 in Covid-19 outpatients. In summary, Covid-19 was associated with hypercholesterolemia, hypertriglyceridemia, and strong endothelial activation. Moreover, the rs670 and rs693 polymorphisms may influence the profile of these parameters in these patients.