O polimorfismo rs187238 no gene da Interleucina-18 está associado a alterações nas Lipoproteínas de alta densidade em pacientes ambulatoriais com COVID-19

Abstract

Covid-19 is an infectious respiratory disease characterized by the excessive production of proinflammatory cytokines, which has led to disorders of multiple organs and systems, with cardiovascular complications being the main cause of death. Interleukin-18 (IL-18) plays an important role in the immunopathogenesis of Covid-19, being associated with endothelial dysfunction and atherosclerotic plaque instability. Among the factors that can influence the production of cytokines, genetic polymorphisms stand out, especially single nucleotide polymorphisms (SNP) which are the most common. Considering the SNPs reported in the IL18 gene, the rs187238 polymorphism impacts the cytosine/guanine (C/G) substitution in the promoter region of the IL-18 gene. Therefore, this study seeks to evaluate the association between the SNP rs187238 and parameters of lipid metabolism in patients with Covid-19 treated in a sentinel unit in Fortaleza-CE. Patient recruitment took place between February and August 2021, nasal secretions were collected from all patients using a nasopharyngeal swab and submitted to the RT-qPCR (quantitative reverse transcription polymerase chain reaction) test to detect SARS-CoV -two. In addition, serum samples were collected to determine total cholesterol (TC), its fractions and triglycerides (TG) by enzymatic-colorimetric assay, apolipoproteins A-I (ApoA-I) and B (ApoB) by immunoturbidimetry and IL-18 by assay. immunoenzymatic (ELISA). Whole blood samples were collected to obtain genomic DNA (gDNA), which was used to analyze the rs187238 SNP using fluorescent TaqMan® probes (VIC - green and FAM - blue) RT-qPCR. Of the 250 patients evaluated, 90 (36%) were positive for Covid-19 and 160 (64%) were negative. Among patients with Covid-19, there was a predominance of females (n = 63; 70.00%), with an average age of 40.29 ± 14.51 years and an average body mass index (BMI) of 27.89 ± 5.81 kg/m², showing a similar distribution between the groups. It was observed that patients with Covid-19 showed a difference in plasma CT levels [183 (151-217) vs. 194 (160.5-237.5) mg/dL] and high-density lipoprotein cholesterol (HDLc) [107 (77–129) vs. 51 (44-60) mg/dL] compared to the concentrations of the Covid-19 negative group. Furthermore, a negative correlation was found between serum levels of IL-18 and HDL-c in patients with Covid-19 (p = 0.0028; r = -0.3169), as well as a positive correlation with the ratio ApoB/A-I, an important marker of cardiovascular risk (p = 0.041; r = 0.217). It was found that patients with CC genotypes would be associated with a reduction in HDL-c (p = 0.029) and ApoA-I (p = 0.047) when affected by Covid-19. Individuals with the G allele and HDL-c levels below 40 mg/dL had higher serum IL-18 levels when exposed to Covid-19. Considering this, it can be concluded that the inflammatory response caused by SARS-CoV-2 in outpatients with Covid-19 can be influenced by the rs187238 SNP and serum HDL-c levels. In the future, other studies may explore the mechanisms that regulate gene expression and the discovery of this work represents an important step towards a deeper understanding of the pathophysiology of the disease.