ArticlePLoS genetics2011
A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 6 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
143 citing papers in PubMed, 6 syntheses or guidelines pooled it, 261 citations in OpenAlex.
- 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
- Genetic variant inAnnals of medicine · 2021Pooled it
- Meta-Analysis of miRNA Variants Associated with Susceptibility to Autoimmune Disease.Disease markers · 2021Pooled it
- Relationship of miRNA-146a to primary Sjögren's syndrome and to systemic lupus erythematosus: a meta-analysis.Rheumatology international · 2017Pooled it
- Association between rs2431697 T allele on 5q33.3 and systemic lupus erythematosus: case-control study and meta-analysis.Clinical rheumatology · 2015Pooled it
- Pooled it
- Genetic variants of microRNA-146a gene: an indicator of systemic lupus erythematosus susceptibility, lupus nephritis, and disease activity.Molecular biology reports · 2020Trial
- Apolipoprotein E Epsilon 4 Enhances the Association between the rs2910164 Polymorphism of miR-146a and Risk of Atherosclerotic Cerebral Infarction.Journal of atherosclerosis and thrombosis · 2016Trial
- Common MIR146A Polymorphisms in Chinese Ankylosing Spondylitis Subjects and Controls.PloS one · 2015Trial
- Association of the miR-146a rs57095329 polymorphism with susceptibility and clinical phenotypes in Parkinson's disease.Neurogenetics · 2026Article
- The Role of Non-coding RNAs in Connective Tissue Diseases: Diagnostic and Therapeutic Potential of miRNAs, lncRNAs and circRNAs.Molecular diagnosis & therapy · 2026Review
- miR-146A and miR-146B Promoter Methylation and Common Sequence Variations Are Not Likely to Be Involved in Autism Spectrum Disorder.Journal of molecular neuroscience : MN · 2025Article
- Association of Epistatic Effects of lncRNA GAS5, miR-146a, IRAK-1, and miR-155 Genetic Variants with Multiple Sclerosis Risk and Severity.Molecular neurobiology · 2025Article
- Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics.Signal transduction and targeted therapy · 2025Review
- Association between genetic variation rs57095329 of microRNA-146a and development of cognitive impairment after anesthesia: a case-control study in a Chinese Han population.Toxicology research · 2025Article
- Regulatory QTLs affecting miRNA-mRNA interactions in cancer: mechanisms, methods, and clinical implications.Frontiers in molecular biosciences · 2025Review
- The 330 risk loci known for systemic lupus erythematosus (SLE): a review.Frontiers in lupus · 2024Article
- The Association of miRNA-146a Gene Variation and Multiple Sclerosis in The Iranian Population.Medical journal of the Islamic Republic of Iran · 2024Article
- MiRNA-146a-A Key Player in Immunity and Diseases.International journal of molecular sciences · 2023Review
- The Role of Genetic Risk Factors in Pathogenesis of Childhood-Onset Systemic Lupus Erythematosus.Current issues in molecular biology · 2023Review
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 5 countries.
Funding
Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic predisposition, characterized by an upregulated type I interferon pathway. MicroRNAs are important regulators of immune homeostasis, and aberrant microRNA expression has been demonstrated in patients with autoimmune diseases. We recently identified miR-146a as a negative regulator of the interferon pathway and linked the abnormal activation of this pathway to the underexpression of miR-146a in SLE patients. To explore why the expression of miR-146a is reduced in SLE patients, we conducted short parallel sequencing of potentially regulatory regions of miR-146a and identified a novel genetic variant (rs57095329) in the promoter region exhibiting evidence for association with SLE that was replicated independently in 7,182 Asians (P(meta) = 2.74×10(-8), odds ratio = 1.29 [1.18-1.40]). The risk-associated G allele was linked to reduced expression of miR-146a in the peripheral blood leukocytes of the controls. Combined functional assays showed that the risk-associated G allele reduced the protein-binding affinity and activity of the promoter compared with those of the promoter containing the protective A allele. Transcription factor Ets-1, encoded by the lupus-susceptibility gene ETS1, identified in recent genome-wide association studies, binds near this variant. The manipulation of Ets-1 levels strongly affected miR-146a promoter activity in vitro; and the knockdown of Ets-1, mimicking its reduced expression in SLE, directly impaired the induction of miR-146a. We also observed additive effects of the risk alleles of miR-146a and ETS1. Our data identified and confirmed an association between a functional promoter variant of miR-146a and SLE. This risk allele had decreased binding to transcription factor Ets-1, contributing to reduced levels of miR-146a in SLE patients.
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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.