ArticleArthritis research & therapy2015
Identification of NF-κB and PLCL2 as new susceptibility genes and highlights on a potential role of IRF8 through interferon signature modulation in systemic sclerosis.
Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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Who cites it
24 citing papers in PubMed, 3 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.Nature communications · 2024Pooled it
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms.Rheumatology international · 2017Pooled it
- Cellular Players in Gastrointestinal Involvement of Systemic Sclerosis: Insights into Pathogenesis.Cells · 2025Review
- Review
- Review
- Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates.Health science reports · 2024Article
- IRF7: role and regulation in immunity and autoimmunity.Frontiers in immunology · 2023Review
- Article
- Article
- Dysregulation of Type 1 Interferon Signaling in Systemic Sclerosis: a Promising Therapeutic Target?Current treatment options in rheumatology · 2021Article
- Updates on genetics in systemic sclerosis.Inflammation and regeneration · 2021Review
- Multi-Ancestry Genome-wide Association Study Accounting for Gene-Psychosocial Factor Interactions Identifies Novel Loci for Blood Pressure Traits.HGG advances · 2021Article
- Chromatin Landscape Underpinning Human Dendritic Cell Heterogeneity.Cell reports · 2020Article
- Role of IRF8 in immune cells functions, protection against infections, and susceptibility to inflammatory diseases.Human genetics · 2020Review
- Extracellular vesicles derived from injured vascular tissue promote the formation of tertiary lymphoid structures in vascular allografts.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Article
- Association of rs4618210A>G variant inJournal of cardiovascular and thoracic research · 2020Article
- Systemic sclerosis and primary biliary cholangitis: An overlapping entity?Journal of scleroderma and related disorders · 2019Review
- Cross-genetic determination of maternal and neonatal immune mediators during pregnancy.Genome medicine · 2018Article
- PhenoRank: reducing study bias in gene prioritization through simulation.Bioinformatics (Oxford, England) · 2018Article
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Authors and funding
18 authors at 14 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionSystemic sclerosis (SSc) and primary biliary cirrhosis (PBC) are rare polygenic autoimmune diseases (AIDs) characterized by fibroblast dysfunction. Furthermore, both diseases share some genetic bases with other AIDs, as evidenced by autoimmune gene pleiotropism. The present study was undertaken to investigate whether single-nucleotide polymorphisms (SNPs) identified by a large genome-wide association study (GWAS) in PBC might contribute to SSc susceptibility.
methodsSixteen PBC susceptibility SNPs were genotyped in a total of 1,616 patients with SSc and 3,621 healthy controls from two European populations (France and Italy).
resultsWe observed an association between PLCL2 rs1372072 (odds ratio (OR) = 1.22, 95% confidence interval (CI) 1.12 to 1.33, P adj = 7.22 × 10(-5)), nuclear factor-kappa-B (NF-κB) rs7665090 (OR = 1.15, 95% CI 1.06 to 1.25, P adj = 0.01), and IRF8 rs11117432 (OR = 0.75, 95% CI 0.67 to 0.86, P adj = 2.49 × 10(-4)) with SSc susceptibility. Furthermore, phenotype stratification showed an association between rs1372072 and rs11117432 with the limited cutaneous subgroup (lcSSc) (P adj = 4.45 × 10(-4) and P adj = 0.001), whereas rs7665090 was associated with the diffuse cutaneous subtype (dcSSc) (P adj = 0.003). Genotype-mRNA expression correlation analysis revealed that the IRF8 protective allele was associated with increased interferon-gamma (IFN-γ) expression (P = 0.03) in patients with SSc but decreased type I IFN (IFIT1) expression in patients and controls (P = 0.02). In addition, we found an epistatic interaction between NF-κB and IRF8 (OR = 0.56, 95% CI 0.00 to 0.74, P = 4 × 10(-4)) which in turn revealed that the IRF8 protective effect is dependent on the presence of the NF-κB susceptibility allele.
conclusionsAn analysis of pleiotropic genes identified two new susceptibility genes for SSc (NF-κB and PLCL2) and confirmed the IRF8 locus. Furthermore, the IRF8 variant influenced the IFN signature, and we found an interaction between IRF8 and NF-κB gene variants that might play a role in SSc susceptibility.
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