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GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients.

ABSTRACT: Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.

SUBMITTER: Mahmoud RH

PROVIDER: S-EPMC8501054 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients.

Mahmoud Rania H RH Hefzy Enas Mamdouh EM Shaker Olfat G OG Ahmed Tarek I TI Abdelghaffar Noha K NK Hassan Essam A EA Ibrahim Amal A AA Ali Doaa Y DY Mohamed Mohamed M MM Abdelaleem Omayma O OO

Scientific reports 20211008 1

Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian populati ...[more]

PMID: 34625583

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Project description:BackgroundHepatitis G virus (HGV) is an RNA virus. It is mainly transmitted through exposure to contaminated blood although other routes may also exist. Patients with chronic renal failure (CRF) are at high risk of acquiring HGV because they require frequent blood transfusions. Ongoing HGV infection can be only diagnosed by demonstrating viremia in patient sample by reverse transcriptase (RT) PCR. Antibodies to the envelop protein E2 (anti E2) of HGV is an indicator of virus clearance and testify past HGV contact. This cross sectional study was done to assess the frequency of HGV exposure (ongoing and past infection) in Egyptian children with CRF and to study the possible risk factors of infection.MethodsThis study included 100 children with CRF [34 on regular haemodialysis (HD) and 66 before the start of dialysis (predialysis)]. All patients sera were tested for HGV RNA by RT-PCR, anti E2, hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (HBcAB). Twenty five healthy children of matched age & sex were used as controls.ResultsHGV RNA was positive in 9 (26.5%) of HD and 9 (13.6%) of predialysis children. Anti E2 was positive in 14 (41.2%) of HD and 19 (28.8%) of predialysis children.In comparison to controls; CRF (n = 100); HD and predialysis children had significantly higher prevalence of anti E2 [4% VS 33% for all CRF cases; (p = 0.002)& 41.2% (p = 0.002) and 28.8% (p = 0.01); for HD and predialysis groups; respectively]. HGV RNA was significantly more prevalent only in HD children in comparison to controls (p = 0.03). HD and predialysis children did not have significant difference in the prevalence of HGV RNA (p = 0.16) or anti E2 (p = 0.26).HGV exposure was not correlated with positivity of anti HCV (p = 0.32), HCV RNA (0.09), HBsAg/HBcAB (p = 1), age (p = 0.06), or gender (p = 0.83). It was significantly correlated with duration of the disease (p < 0.001). Ongoing HGV infection was significantly more prevalent with frequent blood transfusion (p < 0.001). There were no significant differences in serum levels of ALT (p = 0.09), total bilirubin (p = 0.1) and albumin (p = 0.06) in children with ongoing infection in comparison to healthy controls.ConclusionsThe frequency of HGV exposure in Egyptian children with CRF appears to be high and is mainly related to frequent blood transfusions and longer disease duration. HGV infection in these children is not associated with significant changes in hepatic biochemical parameters.

Project description:BackgroundCardiac arrest/cardiopulmonary resuscitation (CA/CPR) represents one of the devastating medical emergencies and is associated with high mortality and neuro-disability. Post-cardiac arrest syndrome (PCAS) is mechanistically ascribed to acute systemic ischemia/reperfusion(I/R) injury. The lncRNA/microRNA/mRNA networks have been found to play crucial roles in the pathogenesis of the hypoxia-responsive diseases. Nonetheless, the precise molecular mechanisms by which lncRNA/miRNA/mRNA axes are involved in the astrocyte-microglia crosstalk in CA/CPR have not been fully elucidated.MethodsWe collected and purified the exosomes from the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. On the basis of microarray analysis, bioinformatic study, and luciferase activity determination, we speculated that lncRNA GAS5/miR-137 is implicated in the astrocyte-microglia crosstalk under the insult of systemic I/R injury. The regulation of lncRNA GAS5/miR-137 on INPP4B was examined by cellular transfection in OGD/R cell culture and by lateral ventricle injection with miR-137 agomir in CA/CPR mice model. Flow cytometry and immunofluorescence staining were performed to detect the microglial apoptosis, M1/M2 phenotype transformation, and neuroinflammation. Neurological scoring and behavior tests were conducted in CA/CPR group, with miR-137 agomir lateral-ventricle infusion and in their controls.ResultsIn all the micRNAs, miR-137 was among the top 10 micRNAs that experienced greatest changes, in both the blood of CA/CPR patients and supernatant of OGD/R-stimulated astrocytes. Bioinformatic analysis revealed that miR-137 was sponged by lncRNA GAS5, targeting INPP4B, and the result was confirmed by Luciferase activity assay. qRT-PCR and Western blotting showed that lncRNA GAS5 and INPP4B were over-expressed whereas miR-137 was downregulated in the blood of CA/CPR patients, OGD/R-stimulated astrocytes, and brain tissue of CA/CPR mice. Silencing lncRNA GAS5 suppressed INPP4B expression, but over-expression of miR-137 negatively modulated its expression. Western blotting exhibited that PI3K and Akt phosphorylation was increased when lncRNA GAS5 was silenced or miR-137 was over-expressed. However, PI3K and Akt phosphorylation was notably suppressed in the absence of miR-137, almost reversing their phosphorylation in the silencing lncRNA GAS5 group. Then we found that GAS5 siRNA or miR-137 mimic significantly increased cell viability and alleviated apoptosis after OGD/R injury. Furthermore, over-expression of miR-137 attenuated microglial apoptosis and neuroinflammation in CA/CPR mice model, exhibiting significantly better behavioral tests after CA/CPR.ConclusionLncRNA GAS5/miR-137 may be involved in the astrocyte-microglia communication that inhibits PI3K/Akt signaling activation via regulation of INPP4B during CA/CPR.

Project description:Background & aimsHepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells highly enriched in the human liver, has not been extensively studied in clinical HDV infection.MethodsMAIT cells from a sizeable cohort of patients with chronic HDV were analyzed ex vivo and in vitro after stimulation. Results were compared with MAIT cells from hepatitis B virus (HBV) monoinfected patients and healthy controls.ResultsCirculating MAIT cells were dramatically decreased in the peripheral blood of HDV-infected patients. Signs of decline were also observed in the liver. In contrast, only a modest decrease of circulating MAIT cells was noted in HBV monoinfection. Unsupervised high-dimensional analysis of residual circulating MAIT cells in chronic HDV infection revealed the appearance of a compound phenotype of CD38hiPD-1hiCD28loCD127loPLZFloEomesloHelioslo cells indicative of activation. Corroborating these results, MAIT cells exhibited a functionally impaired responsiveness. In parallel to MAIT cell loss, HDV-infected patients exhibited signs of monocyte activation and increased levels of proinflammatory cytokines IL-12 and IL-18. In vitro, IL-12 and IL-18 induced an activated MAIT cell phenotype similar to the one observed ex vivo in HDV-infected patients. These cytokines also promoted MAIT cell death, suggesting that they may contribute to MAIT cell activation and subsequent loss during HDV infection.ConclusionsThese results suggest that chronic HDV infection engages the MAIT cell compartment causing activation, functional impairment, and subsequent progressive loss of MAIT cells as the HDV-associated liver disease progresses.Lay summaryHepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. We found that in patients with HDV, a subset of innate-like T cells called mucosa-associated invariant T cells (or MAIT cells), which are normally abundant in peripheral blood and the liver, are activated, functionally impaired and severely depleted.

Dataset Information

GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients.

Publications

GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients.

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