ArticleJournal of the European Academy of Dermatology and Venereology : JEADV2013
DNA methylation of the filaggrin gene adds to the risk of eczema associated with loss-of-function variants.
Article in Journal of the European Academy of Dermatology and Venereology : JEADV, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 83 citations in OpenAlex.
- Skin-lung axis in the atopic march: The immune link from skin to lungs.Chinese medical journal pulmonary and critical care medicine · 2025Review
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- Role of DNA Methylation in the Pathogenesis of Skin Disorders: Mechanisms, Inhibitors of Methylation-Related Enzyme, and Molecular Docking Studies.BioMed research international · 2025Review
- The Effect of Epigenetic Age Acceleration on Atopic Dermatitis: A Mendelian Randomization Study.Clinical, cosmetic and investigational dermatology · 2025Article
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- Multi-Omics Approach to Improved Diagnosis and Treatment of Atopic Dermatitis and Psoriasis.International journal of molecular sciences · 2024Review
- Lipidomics and Metabolomics in Infant Atopic Dermatitis: What's the Correlation with Early Nutrition?Current pediatric reviews · 2024Review
- Genomic, Epigenomic, Transcriptomic, Proteomic and Metabolomic Approaches in Atopic Dermatitis.Current issues in molecular biology · 2023Review
- Intrinsic Effects of Exposome in Atopic Dermatitis: Genomics, Epigenomics and Regulatory Layers.Journal of clinical medicine · 2023Review
- Pathogenesis of allergic diseases and implications for therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- The Genetics of Eczema Herpeticum.Clinical reviews in allergy & immunology · 2022Review
- Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2022Review
- Revisiting the Roles of Filaggrin in Atopic Dermatitis.International journal of molecular sciences · 2022Review
- Epigenetic Mechanisms of Epidermal Differentiation.International journal of molecular sciences · 2022Review
- Epigenetic and metabolic regulation of epidermal homeostasis.Experimental dermatology · 2021Review
- Epigenetics in Non-tumor Immune-Mediated Skin Diseases.Molecular diagnosis & therapy · 2021Review
- Epigenetic Regulation of Epidermal Differentiation.Epigenomes · 2021Review
- DNA Methylation at Birth is Associated with Childhood Serum Immunoglobulin E Levels.Epigenetics insights · 2021Article
- Genetic and Epigenetic Aspects of Atopic Dermatitis.International journal of molecular sciences · 2020Review
- Filaggrin gene mutations with special reference to atopic dermatitis.Current treatment options in allergy · 2020Article
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundLoss-of-function variants within the filaggrin gene (FLG) are associated with a dysfunctional skin barrier that contributes to the development of eczema. Epigenetic modifications, such as DNA methylation, are genetic regulatory mechanisms that modulate gene expression without changing the DNA sequence.
objectivesTo investigate whether genetic variants and adjacent differential DNA methylation within the FLG gene synergistically act on the development of eczema.
methodsA subsample (n = 245, only females aged 18 years) of the Isle of Wight birth cohort participants (n = 1456) had available information for FLG variants R501X, 2282del4 and S3247X and DNA methylation levels for 10 CpG sites within the FLG gene. Log-binomial regression was used to estimate the risk ratios (RRs) of eczema associated with FLG variants at different methylation levels.
resultsThe period prevalence of eczema was 15.2% at age 18 years and 9.0% of participants were carriers (heterozygous) of FLG variants. Of the 10 CpG sites spanning the genomic region of FLG, methylation levels of CpG site 'cg07548383' showed a significant interaction with FLG sequence variants on the risk for eczema. At 86% methylation level, filaggrin haploinsufficient individuals had a 5.48-fold increased risk of eczema when compared to those with wild type FLG genotype (P-value = 0.0008).
conclusionsOur novel results indicated that the association between FLG loss-of-function variants and eczema is modulated by DNA methylation. Simultaneously assessing the joint effect of genetic and epigenetic factors within the FLG gene further highlights the importance of this genomic region for eczema manifestation.
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