ArticleGenome medicine2017
A functional SNP associated with atopic dermatitis controls cell type-specific methylation of the VSTM1 gene locus.
Article in Genome medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Pooled it
- SIRL-1 deficiency reveals pro-inflammatory IL-8 axis in inflammatory bowel disease: a novel diagnostic ratio.Frontiers in immunology · 2026Article
- VSTM1/SIRL-1: An Inhibitory Pattern Recognition Receptor Regulating Myeloid Cells.European journal of immunology · 2025Review
- Role of DNA Methylation in the Pathogenesis of Skin Disorders: Mechanisms, Inhibitors of Methylation-Related Enzyme, and Molecular Docking Studies.BioMed research international · 2025Review
- Lipidomics and Metabolomics in Infant Atopic Dermatitis: What's the Correlation with Early Nutrition?Current pediatric reviews · 2024Review
- New insights into the role of the immune inhibitory receptor VSTM1 in autoimmune disease.Cellular & molecular immunology · 2024Article
- Intrinsic Effects of Exposome in Atopic Dermatitis: Genomics, Epigenomics and Regulatory Layers.Journal of clinical medicine · 2023Review
- Inferring cell-type-specific causal gene regulatory networks during human neurogenesis.Genome biology · 2023Article
- Soluble Signal Inhibitory Receptor on Leukocytes-1 Is Released from Activated Neutrophils by Proteinase 3 Cleavage.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- Multiple datasets to explore the molecular mechanism of sepsis.BMC genomic data · 2022Article
- Signal inhibitory receptor on leukocytes-1 recognizes bacterial and endogenous amphipathic α-helical peptides.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Current understanding of epigenetics in atopic dermatitis.Experimental dermatology · 2021Review
- Genetic Variants in Transcription Factor Binding Sites in Humans: Triggered by Natural Selection and Triggers of Diseases.International journal of molecular sciences · 2021Review
- Leveraging functional annotation to identify genes associated with complex diseases.PLoS computational biology · 2020Article
- Epigenetic alterations in skin homing CD4Scientific reports · 2020Article
- A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter.PloS one · 2020Article
- Resistin expression in human monocytes is controlled by two linked promoter SNPs mediating NFKB p50/p50 binding and C-methylation.Scientific reports · 2019Article
- Convergence of evidence from a methylome-wide CpG-SNP association study and GWAS of major depressive disorder.Translational psychiatry · 2018Article
- Crosstalk of Genetic Variants, Allele-Specific DNA Methylation, and Environmental Factors for Complex Disease Risk.Frontiers in genetics · 2018Review
Corrections and comments
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Authors and funding
34 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExpression quantitative trait loci (eQTL) databases represent a valuable resource to link disease-associated SNPs to specific candidate genes whose gene expression is significantly modulated by the SNP under investigation. We previously identified signal inhibitory receptor on leukocytes-1 (SIRL-1) as a powerful regulator of human innate immune cell function. While it is constitutively high expressed on neutrophils, on monocytes the SIRL-1 surface expression varies strongly between individuals. The underlying mechanism of regulation, its genetic control as well as potential clinical implications had not been explored yet.
methodsWhole blood eQTL data of a Chinese cohort was used to identify SNPs regulating the expression of VSTM1, the gene encoding SIRL-1. The genotype effect was validated by flow cytometry (cell surface expression), correlated with electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP) and bisulfite sequencing (C-methylation) and its functional impact studied the inhibition of reactive oxygen species (ROS).
resultsWe found a significant association of a single CpG-SNP, rs612529T/C, located in the promoter of VSTM1. Through flow cytometry analysis we confirmed that primarily in the monocytes the protein level of SIRL-1 is strongly associated with genotype of this SNP. In monocytes, the T allele of this SNP facilitates binding of the transcription factors YY1 and PU.1, of which the latter has been recently shown to act as docking site for modifiers of DNA methylation. In line with this notion rs612529T associates with a complete demethylation of the VSTM1 promoter correlating with the allele-specific upregulation of SIRL-1 expression. In monocytes, this upregulation strongly impacts the IgA-induced production of ROS by these cells. Through targeted association analysis we found a significant Meta P value of 1.14 × 10
conclusionLow expression of SIRL-1 on monocytes is associated with an increased risk for the manifestation of an inflammatory skin disease. It thus underlines the role of both the cell subset and this inhibitory immune receptor in maintaining immune homeostasis in the skin. Notably, the genetic regulation is achieved by a single CpG-SNP, which controls the overall methylation state of the promoter gene segment.
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