ArticleHepatology (Baltimore, Md.)2015
Polymorphisms in melanoma differentiation-associated gene 5 link protein function to clearance of hepatitis C virus.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Molecular basis of autoimmune disease protection by MDA5 variants.Cell reports · 2025Article
- The HCV-Melanoma Paradox: First Multi-Cohort and Molecular Net-Work Analysis Reveals Lower Incidence but Worse Outcomes-Integrating Clinical, Real-World, and In Silico Data.Medicina (Kaunas, Lithuania) · 2024Article
- Atypical activation of the RNA sensor MDA5 by hepatitis C virus.The FEBS journal · 2024Article
- Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19.Immunogenetics · 2023Article
- Genetic variants of IFIH1 and DHX58 affect the chronicity of hepatitis C in the Chinese Han population.PeerJ · 2023Article
- Uncovering Resistance to Hepatitis C Virus Infection: Scientific Contributions and Unanswered Questions in the Irish Anti-D Cohort.Pathogens (Basel, Switzerland) · 2022Review
- Host genetic susceptibility to viral infections: the role of type I interferon induction.Genes and immunity · 2020Review
- Innate Viral Sensor MDA5 and Coxsackievirus Interplay in Type 1 Diabetes Development.Microorganisms · 2020Review
- Interferon Response in Hepatitis C Virus-Infected Hepatocytes: Issues to Consider in the Era of Direct-Acting Antivirals.International journal of molecular sciences · 2020Review
- Nucleic Acid-Induced Signaling in Chronic Viral Liver Disease.Frontiers in immunology · 2020Review
- Polymorphisms in pattern recognition receptor genes of indigenous and White Leghorn breeds of chicken.Archives animal breeding · 2018Article
- Review
- Severe viral respiratory infections in children withProceedings of the National Academy of Sciences of the United States of America · 2017Article
- The A946T variant of the RNA sensor IFIH1 mediates an interferon program that limits viral infection but increases the risk for autoimmunity.Nature immunology · 2017Article
- An IFIH1 gene polymorphism associated with risk for autoimmunity regulates canonical antiviral defence pathways in Coxsackievirus infected human pancreatic islets.Scientific reports · 2016Article
- Polymorphisms in melanoma differentiation-associated gene 5 are not associated with clearance of hepatitis C virus in a European American population.Hepatology (Baltimore, Md.) · 2016Article
- Recent advances in understanding hepatitis C.F1000Research · 2016Review
- Immunopathogenesis of Hepatitis C Virus Infection.Gastroenterology clinics of North America · 2015Review
- Spontaneous clearance of HCV accompanying hepatitis after liver transplantation.Clinical journal of gastroenterology · 2015Article
- Review
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Authors and funding
18 authors at 8 institutions in 3 countries.
Funding
Abstract
unlabelledAmong patients newly infected with hepatitis C virus (HCV), only 20-30% clear the infection spontaneously. In the remaining 70% the infection persists, causing chronic liver inflammation and disease. It is well established that polymorphisms in host genes, especially in components of the innate immune response, contribute to the phenomenon of spontaneous HCV clearance. Retinoic acid inducible gene-I (RIG-I)-like helicases such as melanoma differentiation-associated gene 5 (MDA-5) are cytoplasmic sensors of viral RNA that are critical for triggering innate immune responses after infection with RNA viruses. We analyzed 14 nonsynonymous single-nucleotide polymorphisms in RIG-I-like helicase-pathway-genes comparing European patients who spontaneously cleared HCV (n = 285) or had persistent infection (n = 509). We found that polymorphic haplotypes in the MDA-5 gene IFIH1 encoding histidine at position 843 and threonine at position 946 strongly correlate with the resolution of HCV infection (odds ratio [OR]: 16.23; 95% confidence interval [CI]: 3.67-71.87; P = 1.1 × 10(-6) ). Overexpression of MDA-5 genetic variants in HEK 293 cells and in a tissue culture model of HCV infection revealed that the histidine 843/threonine 946 variant leads to increased baseline and ligand-induced expression of interferon-induced genes and confers an increased ability to suppress HCV replication.
conclusionThese data suggest that MDA-5 plays a significant role in the defense against HCV and that polymorphisms in MDA-5 can influence the outcome of HCV infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.