Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients

Zayed, Rania A.; Omran, Dalia; Mokhtar, Doha A.; Zakaria, Zinab; Ezzat, Sameera; Soliman, Mohamed A.R.; Mobarak, Lamiaa; El-Sweesy, Hossam; Emam, Ghada Mansour

doi:10.4269/ajtmh.16-0644

Cited by 21 publications

(13 citation statements)

References 61 publications

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“…In addition; there was a non-significant difference between patients and controls as regards age and sex. This was in agreement with Zayed et al [28].…”

Section: Discussionsupporting

confidence: 94%

Evaluation of Plasma Urokinase-Type Plasminogen Activator Receptor and Interleukin 34 in Patients with Chronic Hepatitis C as Serological Fibrosis Markers

Abdulwehab¹,

Ahmed²,

El-Zefzafy³

et al. 2021

OJI

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Background: Hepatitis C Virus (HCV) infection is a progressive disease that may result in chronic hepatitis, fibrosis and cirrhosis. Assessment of liver fibrosis is an essential factor in the management of chronic HCV. Objective: To evaluate plasma soluble Urokinase Plasminogen Activator Receptor (sU-PAR) and interleukin-34 (IL-34) as serological markers of liver fibrosis in patients with chronic HCV. Methods: This case-control study enrolled 60 chronic HCV patients who were subdivided into three groups of mild, moderate and severe hepatic fibrosis depending on Fibrosis-4 score (FIB-4). Patients were compared with 20 age and sex-matched controls. Plasma sUPAR and IL-34 levels were measured by Enzyme Linked Immunosorbent Assay (ELISA). Results: Plasma sUPAR and IL-34 were significantly increased in HCV patients when compared with controls, and their increase was positively correlated with the progression of hepatic fibrosis. Plasma sUPAR and IL-34 positively correlated with Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT), and negatively correlated with hemoglobin concentration and platelet count. The output data of Receiver Operating Characteristic (ROC) curve to differentiate patients from controls revealed that sU-PAR at cut-off > 186.2 ng/L and Area Under Curve (AUC) of 0.944 had (85%) sensitivity and (100%) specificity, and IL-34 at cut off > 16.4 ng/L and AUC of 0.942 had (75%) sensitivity and (100%) specificity. The output data of ROC curve to differentiate severe from mild to moderate hepatic fibrosis patients revealed that sUPAR at cut-off > 510 ng/L and AUC of 0.

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“…In addition; there was a non-significant difference between patients and controls as regards age and sex. This was in agreement with Zayed et al [28].…”

Section: Discussionsupporting

confidence: 94%

Evaluation of Plasma Urokinase-Type Plasminogen Activator Receptor and Interleukin 34 in Patients with Chronic Hepatitis C as Serological Fibrosis Markers

Abdulwehab¹,

Ahmed²,

El-Zefzafy³

et al. 2021

OJI

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“…To the best of our knowledge, these polymorphisms of TLR7 and 9 have not been studied to date with dengue virus infection though TLR9 rs187084 & rs5743836 heterozygous genotype have been found to be significantly associated with neonatal severe hepatitis, neonatal Human Cytomegalovirus infection, malaria, pulmonary tuberculosis and autoimmune diseases [ 3 ]. Similarly, TLR7 rs179008 & rs5743836 are associated with cancer, malaria, HCV, and tuberculosis [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

Study of Single Nucleotide Polymorphisms in Endosomal Toll-Like Receptors-3, 7, and 9 Genes in Patients With Dengue: A Case-Control Study

Singh

Prakash

Garg

et al. 2021

Cureus

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Introduction The endosomal toll-like receptors (TLR) TLR3, TLR7, and TLR9 are localized in immune cells, recognize the viral pattern associated molecular pattern (PAMPs), and start signaling cascades for immune defense response and genetic factor is known to affect the dengue virus infection therefore in our study we study the association of endosomal Toll-like receptors 3 polymorphism rs3775291, rs3775290, and rs3775296 with rs179008 A/T and rs179009C/T polymorphisms of TLR7 and rs187084 (C/T), rs5743836 (C/T) of TLR9 gene with dengue and controls. Materials and methods Ninety-eight cases of dengue virus (DV) infection and 98 healthy controls were enrolled. Clinical details were recorded and cases were classified as severe or non-severe dengue, based on WHO 2009 classification. Genotypes were determined by Sanger sequencing using the genetic analyzer. Results An increased risk of DV infection was observed in cases as compared to controls, with TLR 3 rs3775291 CT genotype (OR = 4.34, P-value: 0.031, CI = 1.14-16.5), Likewise in TLR7 rs179008 AT (OR = 2.12, P-value: 0.034, CI = 1.06-4.26) and rs179009 CT (OR = 2.04, P-value: 0.040, CI = 1.03-4.05) same as in TLR9 rs187084 CT (OR = 1.97, P-value: 0.046, CI = 1.013-3.84) and rs5743836 (OR = 2.38, P-value: 0.009, CI = 1.24-5.57). In the above polymorphisms, mutant allele was observed in a significantly higher number in cases. The values are: for TLR3 rs3775291 T allele (OR 2.167, CI = 1.3-3.61, P-value: 0.003). TLR7 rs179008 T allele (OR 1.90, P-value: 0.021, CI = 1.07-3.35) and in TLR9 rs187084 (OR 1.91, P-value: 0.014, CI = 1.137-3.24) rs5743836 (OR 2.29, P-value: 0.0018, CI = 1.36-3.87). No significant association was observed in the genotypic frequency of severe versus non-severe dengue. Conclusion TLR3, 7, and 9 gene polymorphism might confer host genetic susceptibility to dengue in the North Indian population

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“…TLRs give the innate immune response a considerable specificity of pathogens (6,32,53). HCV core protein interacts with TLRs on monocytes, inducing them to produce cytokines (40).…”

Section: Discussionmentioning

confidence: 99%

TLR3\TLR7 as Differentially Expressed Markers Among Viral, Nonviral, and Autoimmune Diseases in Egyptian Patients

et al. 2021

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Toll-like receptors (TLRs) represent the immune link between the innate and the adaptive immune signals against various pathogens. This study aimed to evaluate the TLRs3 and 7 as immune-markers in differentiating between hepatitis C virus (HCV)-infected and -uninfected patients. Also, the use of the TLR3 and TLR7 as immune markers was compared with the prevalent bio and immune markers for autoimmune diseases in HCVinfected or -uninfected patients. The levels of GPT, GOT, B cell activated factors, tumor necrosis factor-alpha (TNF-a), and interleukin (IL)-10 were measured in plasma, while the levels of TLR3 and TLR7 were quantified in lysates of peripheral blood mononuclear cells from healthy donors, HCV-infected patients, nonalcoholic fatty liver (NAFL) patients without autoimmune diseases and with autoimmune diseases (HCV-infected patients with autoimmune diseases [HCV+auto], nonalcoholic fatty liver patients with autoimmune diseases [NAFL+auto]), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) patients. The relative expression of TLR3, TLR7, TNF, and IL-10 in cell lysates was assessed against glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by quantitative real time-polymerase chain reaction (qRT-PCR). Results showed that TLRs 3 and 7 levels were significantly higher in SLE, RA, HCV, HCV+auto, and the NAFL patients compared to the normal control. The cell lysates from SLE patients expressed TLR3 at relatively significantly higher mRNA levels compared to normal subjects or other patient groups. The NAFL+auto patients expressed TLR7 at relatively significantly high mRNA levels compared to normal subjects or other patients. The RA patients expressed TLR7 at relatively significantly higher mRNA levels when compared to HCV, HCV+auto, and NAFL+auto patients. Conclusions: At the protein level, TLR7 can differentiate between HCV and NAFL patients. In addition, both TLRs3 and 7 can serve as potent markers in differentiating between NAFL and NAFL+auto.

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Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients

Cited by 21 publications

References 61 publications

Evaluation of Plasma Urokinase-Type Plasminogen Activator Receptor and Interleukin 34 in Patients with Chronic Hepatitis C as Serological Fibrosis Markers

Evaluation of Plasma Urokinase-Type Plasminogen Activator Receptor and Interleukin 34 in Patients with Chronic Hepatitis C as Serological Fibrosis Markers

Study of Single Nucleotide Polymorphisms in Endosomal Toll-Like Receptors-3, 7, and 9 Genes in Patients With Dengue: A Case-Control Study

TLR3\TLR7 as Differentially Expressed Markers Among Viral, Nonviral, and Autoimmune Diseases in Egyptian Patients

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