ArticlePloS one2010
Reduced expression of IFIH1 is protective for type 1 diabetes.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 100 citations in OpenAlex.
- ProtectiveiScience · 2026Article
- How loss-of-function mutations inJournal of translational autoimmunity · 2026Review
- Molecular basis of autoimmune disease protection by MDA5 variants.Cell reports · 2025Article
- MDA5 variants trade antiviral activity for protection from autoimmune disease.BMC medical genomics · 2025Article
- Bayesian Effect Size Ranking to Prioritise Genetic Risk Variants in Common Diseases for Follow-Up Studies.Genetic epidemiology · 2025Article
- The perfect storm: unraveling the interplay of genetic predisposition and viral triggers in type 1 diabetes pathogenesis.Frontiers in endocrinology · 2025Review
- Established and Emerging Roles of DEAD/H-Box Helicases in Regulating Infection and Immunity.Immunological reviews · 2025Review
- Investigation of missense mutation-related type 1 diabetes mellitus through integrating genomic databases and bioinformatic approach.Genomics & informatics · 2024Article
- The IFIH1-A946T risk variant promotes diabetes in a sex-dependent manner.Frontiers in immunology · 2024Article
- TheInternational journal of molecular sciences · 2023Article
- Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19.Immunogenetics · 2023Article
- Is the Association of the Rare rs35667974 IFIH1 Gene Polymorphism With Autoimmune Diseases a Case of RNA Epigenetics?Journal of molecular evolution · 2023Article
- MDA5-dependent responses contribute to autoimmune diabetes progression and hindrance.JCI insight · 2023Article
- Article
- Unravelling the Proteomics of HLA-B*57:01Journal of personalized medicine · 2022Article
- Functional Impact of Risk Gene Variants on the Autoimmune Responses in Type 1 Diabetes.Frontiers in immunology · 2022Review
- Nrf2 activator PB125® as a carnosic acid-based therapeutic agent against respiratory viral diseases, including COVID-19.Free radical biology & medicine · 2021Review
- Role of nucleic acid sensing in the pathogenesis of type 1 diabetes.World journal of diabetes · 2021Review
- Innate Viral Sensor MDA5 and Coxsackievirus Interplay in Type 1 Diabetes Development.Microorganisms · 2020Review
- Advances in Knowledge of Candidate Genes Acting at the Beta-Cell Level in the Pathogenesis of T1DM.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
IFIH1 (interferon induced with helicase C domain 1), also known as MDA5 (melanoma differentiation-associated protein 5), is one of a family of intracellular proteins known to recognise viral RNA and mediate the innate immune response. IFIH1 is causal in type 1 diabetes based on the protective associations of four rare variants, where the derived alleles are predicted to reduce gene expression or function. Originally, however, T1D protection was mapped to the common IFIH1 nsSNP, rs1990760 or Thr946Ala. This common amino acid substitution does not cause a loss of function and evidence suggests the protective allele, Ala(946), may mark a haplotype with reduced expression of IFIH1 in line with the protection conferred by the four rare loss of function alleles. We have performed allele specific expression analysis that supports this hypothesis: the T1D protective haplotype correlates with reduced IFIH1 transcription in interferon-β stimulated peripheral blood mononuclear cells (overall p = 0.012). In addition, we have used multiflow cytometry analysis and quantitative PCR assays to prove reduced expression of IFIH1 in individuals heterozygous for three of the T1D-associated rare alleles: a premature stop codon, rs35744605 (Glu627X) and predicted splice variants, rs35337543 (IVS8+1) and rs35732034 (IVS14+1). We also show that the nsSNP, Ile923V, does not alter pre-mRNA levels of IFIH1. These results confirm and extend the new autoimmune disease pathway of reduced IFIH1 expression and protein function protecting from T1D.
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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.