ABSTRACT
BACKGROUND: Several epidemiological studies have suggested that genetic variations in encoding pattern recognition receptors (PRRs) genes such as Toll Like Receptors (TLRs) and their signaling products, may influence the susceptibility, severity and outcome of tuberculosis (TB). After sensing a pathogen, the cell responds producing an inflammatory response, to restrain the pathogen's successful course of infection. Herein we assessed single nucleotide polymorphisms (SNP) and gene expression from pathogen recognition and inflammasome pathways in Brazilian TB patients. METHODS AND RESULTS: For genetic association analysis we included MYD88 and TLR4, PRRs sensing proteins. Allele distribution for MYD88 rs6853 (A > G) and TLR4 rs7873784 (C > G) presented conserved among the tested samples with statistically differential distribution in TB patients versus controls. However, when testing according to sample ethnicity (African or Caucasian-derived individuals) we identified that the rs6853 G/G genotype was associated with a lower susceptibility to TB in Caucasian population. Meanwhile, the rs7873784 G/G genotype was associated with a higher TB susceptibility in Afro-descendant ethnicity individuals. We also aimed to verify MYD88 and the inflammasome genes NLRP1 and NLRC4 expression in order to connect to active TB and/or clinical aspects. CONCLUSIONS: We identified that inflammasome gene expression in TB patients under treatment display a similar pattern as in healthy controls, indicating that TB treatment impairs NLRP1 inflammasome activation.
Subject(s)
Inflammasomes , Myeloid Differentiation Factor 88 , Humans , Inflammasomes/genetics , Myeloid Differentiation Factor 88/genetics , Toll-Like Receptor 4 , Undertreatment , Adaptor Proteins, Signal Transducing , Gene ExpressionABSTRACT
Metabolic syndrome (MS) is a set of clinical conditions such as insulin resistance, hyperglycemia, systemic arterial hypertension (SAH), dyslipidemia, obesity and high abdominal circumference. Some of these clinical characteristics have been associated with caveolin-1, a caveolae structural protein, responsible for insulin activation, storage and degradation of cholesterol, and so on. Herein we assessed CAV-1 mRNA levels in MS patients comparing to healthy controls (HC) and according patients' clinical features. We included 87 patients in the study, 25 patients with MS, 30 patients with at least one clinical condition (diabetes, SAH, dyslipidemia, obesity and high abdominal circumference), 13 with two clinical conditions and 19 HC. CAV-1 mRNA levels from peripheral blood samples were assessed by Real Time qPCR using specific Taqman probe. The analysis was performed using ∆Cq method and the statistical tests Shapiro-Wilk, One-Way ANOVA and Mann-Whitney. We found CAV-1 increased mRNA levels in patients with MS (1.645 FC, p = 9.794 × 10-20) and even higher in patients with only one or two clinical conditions (2.215 FC, p = 1.215 × 10-32 and 1.716 FC, p = 4.197 × 10-05, respectively). When individual clinical conditions were observed, individuals with high abdominal circumference and obesity present a significantly up regulation when compared to HC (2.956 FC, p = 0.0004 and 3.643 FC, p = 0.002, respectively). This work indicates that CAV-1 gene expression from whole blood samples is associated to MS clinical conditions and may become a potential target for MS treatment and prevention.
Subject(s)
Caveolin 1/genetics , Metabolic Syndrome/genetics , RNA, Messenger/genetics , Up-Regulation , Adult , Aged , Analysis of Variance , Case-Control Studies , Cross-Sectional Studies , Female , Gene Expression Regulation , Humans , Insulin Resistance/genetics , Male , Metabolic Syndrome/blood , Metabolic Syndrome/metabolism , Middle Aged , Obesity/genetics , RNA, Messenger/metabolismABSTRACT
BACKGROUND AND AIMS: The outbreak of the new coronavirus, SARS-CoV-2, causes a respiratory disease and individuals with pre-existing cardiometabolic disorders display worse prognosis through the infection course. The aim of this minireview is to present epidemiological data related to metabolic comorbidities in association with the SARS-CoV-2. METHODS: This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. RESULTS: Studies indicate that obese individuals are more likely to develop infections, and that adipose tissue serves as a pathogen reservoir. In diabetic individuals higher rate of inflammatory processes is seen due to constant glucose recognition by C type lectin receptors. Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human's cell entry. Until now, the studies have shown that individuals with those conditions and affected by COVID-19 present an uncontrolled release of pro-inflammatory cytokines and an unbalanced immune response, leading to the cytokine storm phenomenon. Vitamin D is highlighted as a potential therapeutic target, because in addition to acting on the immune system, it plays an important role in the control of cardiometabolic diseases. CONCLUSION: Currently, since there is no proven and effective antiviral therapy for SARS-CoV-2, the efforts should focus on controlling inflammatory response and reduce the risks of associated complications.
