ArticleAnnals of the rheumatic diseases2016
The genetic association of RUNX3 with ankylosing spondylitis can be explained by allele-specific effects on IRF4 recruitment that alter gene expression.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- Replication study and meta-analysis indicate a suggestive association of RUNX3 locus with primary biliary cholangitis.Immunogenetics · 2020Pooled it
- Interferon regulatory factors orchestrate CD8International journal of molecular medicine · 2026Review
- Biomarkers in axial spondyloarthritis diagnosis: from clinical signs to multi-omics integration.Frontiers in immunology · 2026Review
- Editorial: Transcriptional and posttranscriptional homeostasis in inflammation and inflammatory diseases.Frontiers in immunology · 2024Article
- Comprehensive epigenomic profiling reveals the extent of disease-specific chromatin states and informs target discovery in ankylosing spondylitis.Cell genomics · 2023Article
- Chromosome conformation capture approaches to investigate 3D genome architecture in Ankylosing Spondylitis.Frontiers in genetics · 2023Article
- Methylation ofGenes · 2022Article
- Monocytes and Macrophages in Spondyloarthritis: Functional Roles and Effects of Current Therapies.Cells · 2022Review
- Functional Genomic Analysis of a RUNX3 Polymorphism Associated With Ankylosing Spondylitis.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- Disruption of c-MYC Binding and Chromosomal Looping Involving Genetic Variants Associated With Ankylosing Spondylitis Upstream of theFrontiers in genetics · 2021Article
- DNA Methylation Signature in Monozygotic Twins Discordant for Psoriatic Disease.Frontiers in cell and developmental biology · 2021Article
- Perspectives on the Genetic Associations of Ankylosing Spondylitis.Frontiers in immunology · 2021Review
- The Genetics of Spondyloarthritis.Journal of personalized medicine · 2020Review
- Revisiting the gut-joint axis: links between gut inflammation and spondyloarthritis.Nature reviews. Rheumatology · 2020Review
- RUNX3 Polymorphisms Affect the Risk of Ankylosing Spondylitis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Potential T Cell-Intrinsic Regulatory Roles for IRF5 via Cytokine Modulation in T Helper Subset Differentiation and Function.Frontiers in immunology · 2020Review
- Article
- Ankylosing spondylitis: etiology, pathogenesis, and treatments.Bone research · 2019Article
- IL-17 in the immunopathogenesis of spondyloarthritis.Nature reviews. Rheumatology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
objectivesTo identify the functional basis for the genetic association of single nucleotide polymorphisms (SNP), upstream of the RUNX3 promoter, with ankylosing spondylitis (AS).
methodsWe performed conditional analysis of genetic association data and used ENCODE data on chromatin remodelling and transcription factor (TF) binding sites to identify the primary AS-associated regulatory SNP in the RUNX3 region. The functional effects of this SNP were tested in luciferase reporter assays. Its effects on TF binding were investigated by electrophoretic mobility gel shift assays and chromatin immunoprecipitation. RUNX3 mRNA levels were compared in primary CD8+ T cells of AS risk and protective genotypes by real-time PCR.
resultsThe association of the RUNX3 SNP rs4648889 with AS (p<7.6×10(-14)) was robust to conditioning on all other SNPs in this region. We identified a 2 kb putative regulatory element, upstream of RUNX3, containing rs4648889. In reporter gene constructs, the protective rs4648889 'G' allele increased luciferase activity ninefold but significantly less activity (4.3-fold) was seen with the AS risk 'A' allele (p≤0.01). The binding of Jurkat or CD8+ T-cell nuclear extracts to the risk allele was decreased and IRF4 recruitment was reduced. The AS-risk allele also affected H3K4Me1 histone methylation and associated with an allele-specific reduction in RUNX3 mRNA (p<0.05).
conclusionWe identified a regulatory region upstream of RUNX3 that is modulated by rs4648889. The risk allele decreases TF binding (including IRF4) and reduces reporter activity and RUNX3 expression. These findings may have important implications for understanding the role of T cells and other immune cells in AS.
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