RESUMEN
It is predictable that the renin-angiotensin-aldosterone and kinin-kallikrein systems are dysregulated in COVID-19 (COV) patients because SARS-CoV-2 requires ACE2 to cause an infection. This study aimed to assess the serum levels of des-arg(9)-bradykinin (DABK) and angiotensin 1-7 (ang-(1-7)) in patients with COV who had the above-mentioned cardiovascular disease risk factors. In a cross-sectional study, 69 COV patients were selected among patients referred to the main referral center for these patients, in Kerman, Iran, and 73 matched control (non-COV) individuals among individuals who participated in the KERCARD cohort study. Serum levels of DABK and ang-(1-7) were measured by ELISA in the groups of CTL (healthy), HTN, DM, OB, COV, COV + HTN, COV + DM, and COV + OB. Ang-(1-7) levels were lower in the COV + HTN group compared to the HTN group. DABK levels were higher in the COV, HTN, and OB groups and in DM + COV subjects compared to their corresponding control group. The levels of ang-(1-7) and DABK were related to HTN and OB, respectively. According to the findings, we can infer that an increase in DABK production in those with the cardiovascular disease risk factors of diabetes, obesity, and hypertension or a decrease in ang-(1-7) in those with hypertension may contribute to the adverse outcomes of SARS-CoV-2 infection.
RESUMEN
Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00-5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30-6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97-5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62-4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37-2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.
