ArticleNature communications2021
SLE non-coding genetic risk variant determines the epigenetic dysfunction of an immune cell specific enhancer that controls disease-critical microRNA expression.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 3 of them syntheses that pooled it.
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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
46 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Association between Susceptibility to Systemic Lupus Erythematous and Polymorphisms in miR-146a and miR-499: A Meta-Analysis.International archives of allergy and immunology · 2023Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Genetic variant inAnnals of medicine · 2021Pooled it
- Epigenetic pacemaker: A review of DNA methylation, histone lactylation, and non-coding RNAs in autoimmune skin diseases.Journal of translational autoimmunity · 2026Review
- miR-146a mimic therapy protects against platelet-mediated thrombosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Circulating miRNAs as Biomarkers of Tick-Borne Encephalitis Severity: Association with Cytokine Profile in Febrile, Meningeal, and Encephalitic Forms.International journal of molecular sciences · 2026Article
- Sex matters: mechanistic insights into sex-driven patterns of autoimmunity and implications for pharmacotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Systemic lupus erythematosus-accelerated atherosclerosis: mechanistic insights and clinical implications.Frontiers in immunology · 2026Review
- The rs713586 risk variant dysregulates ADCY3 rather than DNAJC27, leading to obesity through ZFP42-TET1-mediated DNA methylation.EBioMedicine · 2026Article
- LncRNA PVT1 regulates CD4 + T cell dysregulation in systemic lupus erythematosus: insights from human patients and MRL/lpr mouse.Clinical rheumatology · 2025Article
- An overview on Sjögren's syndrome and systemic lupus erythematosus' genetics.Toxicology research · 2025Review
- Exploring the role of APRIL in autoimmunity: implications for therapeutic targeting in systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome.Frontiers in immunology · 2025Review
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
- Functional Genomics in Psoriasis.International journal of molecular sciences · 2024Review
- Decoding Non-coding Variants: Recent Approaches to Studying Their Role in Gene Regulation and Human Diseases.Frontiers in bioscience (Scholar edition) · 2024Review
- Role of microRNAs in Immune Regulation with Translational and Clinical Applications.International journal of molecular sciences · 2024Review
- MicroRNA-125b mediates Interferon-γ-induced downregulation of the vitamin D receptor in systemic lupus erythematosus.Zeitschrift fur Rheumatologie · 2024Article
- Serum Metabolic Fingerprints Characterize Systemic Lupus Erythematosus.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mapping theme evolution and identifying hotspots in biomarkers of systemic lupus erythematosus based on global research.Biomarkers in medicine · 2024Article
- Explore the shared molecular mechanism between dermatomyositis and nasopharyngeal cancer by bioinformatic analysis.PloS one · 2024Article
Corrections and comments
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Authors and funding
25 authors.
Funding
Abstract
Since most variants that impact polygenic disease phenotypes localize to non-coding genomic regions, understanding the consequences of regulatory element variants will advance understanding of human disease mechanisms. Here, we report that the systemic lupus erythematosus (SLE) risk variant rs2431697 as likely causal for SLE through disruption of a regulatory element, modulating miR-146a expression. Using epigenomic analysis, genome-editing and 3D chromatin structure analysis, we show that rs2431697 tags a cell-type dependent distal enhancer specific for miR-146a that physically interacts with the miR-146a promoter. NF-kB binds the disease protective allele in a sequence-specific manner, increasing expression of this immunoregulatory microRNA. Finally, CRISPR activation-based modulation of this enhancer in the PBMCs of SLE patients attenuates type I interferon pathway activation by increasing miR-146a expression. Our work provides a strategy to define non-coding RNA functional regulatory elements using disease-associated variants and provides mechanistic links between autoimmune disease risk genetic variation and disease etiology.
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