Tumor necrosis factor-alpha (TNF-α) is an important cytokine in generating an immune response against infection with hepatitis C virus (HCV). The functions of TNF-α may be altered by single-nucleotide polymorphisms ...Tumor necrosis factor-alpha (TNF-α) is an important cytokine in generating an immune response against infection with hepatitis C virus (HCV). The functions of TNF-α may be altered by single-nucleotide polymorphisms (SNPs) in its gene structure. We hypothesized that SNPs in TNF-α may be important in determining the outcome of an HCV infection. To test this hypothesis, we investigated the role of the polymorphism -308G/A, which is located in the promoter region of the TNF-α gene, in the progression of HCV infection in Egyptian patients using a quantitative real-time polymerase chain reaction (qRT-PCR). The distribution of this polymorphism and its impact on the serum level of TNF-α was compared between 90 HCV-infected patients [45 with HCV-induced cirrhosis and 45 with HCV-related hepatocellular carcinoma (HCC)] and 45 healthy Egyptian volunteers without any history of liver disease. Our results showed that at the TNF-α -308 position, the G/G allele was most common (78.5% ) in the study population, with the G/A and A/A alleles occurring less frequently (13.3% and 8.1% , respectively). Frequencies of G/G, G/A, and A/A genotypes were 87%, 7%, and 6% in patients with liver cirrhosis and were 94% , 4% , and 2% in patients with HCC, respectively. Serum levels of TNF-α were significantly higher in HCV-infected patients than in healthy controls, indicating that the TNF-α -308 polymorphism does not influence the production of TNF-α. The serum level of TNF-α was positively correlated with HCV infection. Taken together, these findings suggest that the TNF-α -308 polymorphism may not be a host genetic factor associated with the severity of HCV infection, but may be an independent risk factor for HCC.展开更多
Objective MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases.HypoxamiRs(miR-210 and miR-21)play an important role in hypoxia and in inflammation-associa...Objective MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases.HypoxamiRs(miR-210 and miR-21)play an important role in hypoxia and in inflammation-associated hypoxia.Systemic lupus erythematosus(SLE)is a chronic systemic autoimmune disease that would potentiate many pathological complications,including hemolytic anemia.This study aimed to investigate the role of hypoxamiRs in SLE/hemolytic anemia patients.Methods This work was designed to analyze the circulating levels of↱the miR-210 and miR-21 expressions and hypoxia-inducible factor-1α(HIF-α)in SLE/hemolytic anemia patients.SLE activity was evaluated for all patients by SLE Disease Activity Index(SLEDAI).Clinical manifestations/complications and serological/hematological investigations were reported.HIF-αconcentration was assayed by ELISA and expression of miR-21 and miR-210 was analyzed by qRT-PCR.Results The results indicated that the fold change of the miR-210/miR-21 expressions in plasma was significantly elevated in SLE/hemolytic anemia patients.A strong positive correlation between the miR-210 and miR-21 expression levels was also recorded.Among the associated-disease complications,hypertension,arthritis,oral ulcers,and serositis were associated with a high circulating miR-210 expression,while the occurrence of renal disorders was associated with the increased miR-21 expression.Furthermore,the HIF-αlevel was remarkably elevated in SLE/hemolytic anemia patients.A high positive correlation was recorded between the HIF-αconcentration and miR-210/miR-21 expression levels.The occurrence of oral ulcers,arthritis,and hypertension was associated with the increased HIF-αconcentration.On the other hand,SLEDAI and white blood cell count were positively correlated with miR-21/miR-210.The erythrocyte sedimentation rate was positively correlated with miR-21.Conclusion The dysregulation of the circulating miR-210/miR-210/HIF-1αlevels in SLE/hemolytic anemia patients advocated that the hypoxia pathway might have an essential role in the pathogenesis and complications of these diseases.展开更多
文摘Tumor necrosis factor-alpha (TNF-α) is an important cytokine in generating an immune response against infection with hepatitis C virus (HCV). The functions of TNF-α may be altered by single-nucleotide polymorphisms (SNPs) in its gene structure. We hypothesized that SNPs in TNF-α may be important in determining the outcome of an HCV infection. To test this hypothesis, we investigated the role of the polymorphism -308G/A, which is located in the promoter region of the TNF-α gene, in the progression of HCV infection in Egyptian patients using a quantitative real-time polymerase chain reaction (qRT-PCR). The distribution of this polymorphism and its impact on the serum level of TNF-α was compared between 90 HCV-infected patients [45 with HCV-induced cirrhosis and 45 with HCV-related hepatocellular carcinoma (HCC)] and 45 healthy Egyptian volunteers without any history of liver disease. Our results showed that at the TNF-α -308 position, the G/G allele was most common (78.5% ) in the study population, with the G/A and A/A alleles occurring less frequently (13.3% and 8.1% , respectively). Frequencies of G/G, G/A, and A/A genotypes were 87%, 7%, and 6% in patients with liver cirrhosis and were 94% , 4% , and 2% in patients with HCC, respectively. Serum levels of TNF-α were significantly higher in HCV-infected patients than in healthy controls, indicating that the TNF-α -308 polymorphism does not influence the production of TNF-α. The serum level of TNF-α was positively correlated with HCV infection. Taken together, these findings suggest that the TNF-α -308 polymorphism may not be a host genetic factor associated with the severity of HCV infection, but may be an independent risk factor for HCC.
基金supported by the Taif University Researchers Supporting Project(No.TURSP-2020/103).
文摘Objective MicroRNAs are fine regulators for gene expression during the post-transcriptional stage in many autoimmune diseases.HypoxamiRs(miR-210 and miR-21)play an important role in hypoxia and in inflammation-associated hypoxia.Systemic lupus erythematosus(SLE)is a chronic systemic autoimmune disease that would potentiate many pathological complications,including hemolytic anemia.This study aimed to investigate the role of hypoxamiRs in SLE/hemolytic anemia patients.Methods This work was designed to analyze the circulating levels of↱the miR-210 and miR-21 expressions and hypoxia-inducible factor-1α(HIF-α)in SLE/hemolytic anemia patients.SLE activity was evaluated for all patients by SLE Disease Activity Index(SLEDAI).Clinical manifestations/complications and serological/hematological investigations were reported.HIF-αconcentration was assayed by ELISA and expression of miR-21 and miR-210 was analyzed by qRT-PCR.Results The results indicated that the fold change of the miR-210/miR-21 expressions in plasma was significantly elevated in SLE/hemolytic anemia patients.A strong positive correlation between the miR-210 and miR-21 expression levels was also recorded.Among the associated-disease complications,hypertension,arthritis,oral ulcers,and serositis were associated with a high circulating miR-210 expression,while the occurrence of renal disorders was associated with the increased miR-21 expression.Furthermore,the HIF-αlevel was remarkably elevated in SLE/hemolytic anemia patients.A high positive correlation was recorded between the HIF-αconcentration and miR-210/miR-21 expression levels.The occurrence of oral ulcers,arthritis,and hypertension was associated with the increased HIF-αconcentration.On the other hand,SLEDAI and white blood cell count were positively correlated with miR-21/miR-210.The erythrocyte sedimentation rate was positively correlated with miR-21.Conclusion The dysregulation of the circulating miR-210/miR-210/HIF-1αlevels in SLE/hemolytic anemia patients advocated that the hypoxia pathway might have an essential role in the pathogenesis and complications of these diseases.