👤 Nadia M Hamdy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), which is a huge global health threat. Interleukin27 (IL-27) gene is a cytokine that produces antiviral proteins in an IFN-independent manner and stimulates both pro- and anti-inflammatory responses. Interferon induced transmembrane protein 3 (IFITM3) inhibits SARS-CoV2 infection by blocking SARSCoV-2 spike proteins which facilitate viral entrance and cell-to-cell fusion. The association between genetic variants and COVID-19 in Egyptians is still unclear. Hence, we sought to investigate the impact of the single nucleotide polymorphism of IL-27P28 rs153109 and IFITM3 rs12252 on the susceptibility and severity of SARS-CoV-2 in Egyptian patients. Our study included 242 SARS-CoV-2 patients were recruited from Main University Hospital, Alexandria University, Egypt, and 187 healthy controls. We subdivided the patient group into two subgroups: group A comprised mild/moderate cases (N = 42) (17.4%), and group B included severe/critical cases (N = 200) (82.6%). Genomic DNA was extracted from blood samples using the QIAamp DNA Blood Mini kit, then the PCR products of IL27 and IFITM3 were cut by FastDigest XhoI and MScI, respectively, for detection of SNPs of IL-27P28 rs153109 (-964A/G) and IFITM3 rs12252 (T>C). The present study found a significant association between IL27 rs153109 (-964A/G) and SARS-CoV-2 infection susceptibility after adjusting for the risk factor (advanced age), IL27 rs153109 (-964A/G) AG genotype (OR = 2.791, 95% CI: 1.237-6.295, P = 0.013), AA genotype (OR = 2.385, 95% CI: 1.075-5.291, P = 0.033), and (AG+AA vs. GG) genotypes (OR = 2.558, 95% CI: 1.186-5.517, P = 0.017). On the other hand, the IFITM3 rs12252(T>C) CT genotype (OR = 1.419, 95% CI: 0.843-2.391, P = 0.188), CC genotype (OR = 2.132, 95% CI: 0.436-10.415, P = 0.350), and (C/T+C/C vs. TT) genotypes (OR = 1.466, 95% CI: 0.884-2.432, P = 0.138) did not show a statistically significant association with either susceptibility or the severity of SARS-CoV-2. IL27P28 rs153109 AG and AA genotypes of IL27 may be associated with the susceptibility of SARS-CoV-2 infection but not the severity. Concerning the IFITM3 rs12252 SNP, we could not confirm its influence on either susceptibility or the severity of SARS-CoV-2 in this Egyptian population. Show less

A promising treatment for obesity involves the use of therapeutic agents that increase the level of the glucagon-like peptide (GLP-1) which reduces appetite and food intake. Native GLP-1 is rapidly metabolized by the dipeptidyl peptidase-4 (DPP-4) enzyme and, as such, GLP-1 mimetics or DPP-4 inhibitors represent promising treatment approaches. Interestingly, obese patient receiving such medications showed improved lipid profiles and cholesterol homeostasis, however the mechanism(s) involved are not known. Members of the ATP-binding cassette (ABC) transporters, including ABCA1 and ABCG1, play essential roles in reverse cholesterol transport and in high density lipoprotein (HDL) formation. These transporters are under the transcriptional regulation of liver X receptor alpha (LXR-α). We hypothesize that GLP-1 mimetics and/or DPP-4 inhibitors modulate ABCA1/ABCG1 expression in adipocytes through an LXR-α mediated process and thus affecting cholesterol homeostasis. 3T3-L1 adipocytes were treated with the DPP-4 inhibitor vildagliptin (2 nM) or the GLP-1 mimetic exendin-4 (5 nM). Gene and protein expression of ABCA1, ABCG1 and LXR-α were determined and correlated with cholesterol efflux. Expression levels of interleukin-6 (IL-6), leptin and the glucose transporter-4 (GLUT-4) were also determined. Treatment with both medications significantly increased the expression of ABCA1, ABCG1, LXR-α and GLUT-4, decreased IL-6 and leptin, and improved cholesterol efflux from adipocytes (P < 0.05). Our data suggest that GLP-1-based therapy modulate ABCA1/ABCG1 expression in adipocytes potentially through an LXR-α mediated process. Show less