ABSTRACT
Hashimoto's thyroiditis (HT) and Graves' disease (GD) susceptibility depends on a complex interaction between environmental and genetic factors. Genes for tumor necrosis factor alpha (TNF-α) and toll-like receptors (TLRs) have been incorporated into the pathophysiology of autoimmune disorders. Our aim is to assess the association between TLR7 (rs179009) and TNF-α (rs1800629) polymorphisms and susceptibility to autoimmune thyroid disorders. One-hundred ninety-nine individuals, divided into 68 HT patients in group I, 57 GD patients in group II, and 74 age- and gender-matched healthy subjects in group III, underwent laboratory investigations, including the detection of TLR7 and TNF-α polymorphisms using real-time PCR technique. TLR7 (rs179009) genotypes, A/G and G/G, were significantly more prevalent in HT patients (group I) compared to normal controls. Meanwhile, TNF-α (rs1800629) genotypes in GD patients (group II) showed a six fold increase in the risk of the disease in the G/A and A/A genotypes. Our findings propose the fact that the polymorphisms of TLR7 (rs179009) play a role in the susceptibility and the development of Hashimoto's thyroiditis, whereas TNF-α (rs1800629) polymorphisms play a role in the susceptibility and development of Graves' disease.
Subject(s)
Autoimmune Diseases , Graves Disease , Hashimoto Disease , Humans , Egypt , Genetic Predisposition to Disease/genetics , Graves Disease/genetics , Graves Disease/pathology , Hashimoto Disease/genetics , Polymorphism, Single Nucleotide/genetics , Toll-Like Receptor 7/genetics , Tumor Necrosis Factor-alpha/geneticsABSTRACT
BACKGROUND: COVID-19 is a novel infectious disease for which no specific treatment exists. It is likely that a combination of genetic and non-genetic factors predispose to it. Expression levels of genes that are involved in the interaction with SARS-CoV-2 or the host response are thought to play a role in disease susceptibility and severity. It is crucial to explore biomarkers for disease severity and outcome. Herein, we studied the expression levels and effects of long non-coding metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) and long non-coding maternally expressed gene 3 (lnc-MEG3) in COVID-19 patients. The study enrolled 35 hospitalized and 35 non-hospitalized COVID-19 patients, and 35 healthy controls. A chest computed tomography (CT) scan, complete blood count (CBC), ferritin, C-reactive protein (CRP), D-dimer and analysis of lnc-MALAT1 and lnc-MEG3 expression were done. RESULTS: There was a significant relation between ferritin, CRP, D-dimer levels, oxygen saturation, CT-CORADS score and disease severity. Lnc-MALAT1 was significantly higher but lnc-MEG3 was significantly lower in patients vs. controls, and in hospitalized vs. non-hospitalized patients. Elevated MALAT1 and reduced MEG3 levels were significantly associated with more elevated ferritin, CRP, D-dimer levels, lower oxygen saturation, higher CT-CORADS score and poor survival. Moreover, MALAT1 and MEG3 levels displayed higher sensitivity and specificity as predictors of COVID-19 severity compared with other prognostic biochemical markers such as ferritin, CRP, and D-dimer. CONCLUSIONS: MALAT1 levels are higher, whereas MEG3 levels are lower in COVID-19 patients. Both are linked to disease severity and mortality and could emerge as predictive biomarkers for COVID-19 severity and therapeutic targets.
