ArticleProceedings of the National Academy of Sciences of the United States of America2014
Genetic-epigenetic dysregulation of thymic TSH receptor gene expression triggers thyroid autoimmunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed.
- Clinical efficacy of Yingliu mixture combined with metimazole for treating diffuse goitre with hyperthyroidism and its impact on related cytokines.Pharmaceutical biology · 2017Trial
- Cell-intrinsic functions of PD-L1 activate autophagy and prevent cytokine-induced apoptosis.Science advances · 2026Article
- Epigenetic regulation of nuclear receptors: Implications for endocrine-related diseases and therapeutic strategies.Genes & diseases · 2025Review
- Lower dietary folate intake increases the risk of autoimmune thyroiditis.Frontiers in nutrition · 2025Article
- Exploring antigenic variation in autoimmune endocrinopathy.Frontiers in immunology · 2025Review
- Recent advances in anterior pituitary hormones and metabolic-associated fatty liver disease.Frontiers in endocrinology · 2025Review
- Fibrocyte Participation in Thyroid-Associated Ophthalmopathy Suggests New Approaches to Therapy.Ophthalmic plastic and reconstructive surgery · 2023Review
- Review
- Genetics and epigenetics of autoimmune thyroid diseases: Translational implications.Best practice & research. Clinical endocrinology & metabolism · 2023Review
- Article
- Iron: Not Just a Passive Bystander in AITD.Nutrients · 2022Review
- The multifaceted functional role of DNA methylation in immune-mediated rheumatic diseases.Clinical rheumatology · 2021Review
- Emerging Insights Into the Role of Epigenetics and Gut Microbiome in the Pathogenesis of Graves' Ophthalmopathy.Frontiers in endocrinology · 2021Review
- Epigenetics effect on pathogenesis of thyroid-associated ophthalmopathy.International journal of ophthalmology · 2021Review
- Epigenetic Regulations of AhR in the Aspect of Immunomodulation.International journal of molecular sciences · 2020Review
- Graves' disease.Nature reviews. Disease primers · 2020Review
- Review
- Review
- A Mouse Thyrotropin Receptor A-Subunit Transgene Expressed in Thyroiditis-Prone Mice May Provide Insight into Why Graves' Disease Only Occurs in Humans.Thyroid : official journal of the American Thyroid Association · 2019Article
- A Modifying Autoantigen in Graves' Disease.Endocrinology · 2019Article
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9 authors.
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Abstract
Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNα, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261 site. Repression by PLZF depended on the rs12101261 disease susceptibility allele and was increased by IFNα. Intrathymic TSHR expression was decreased in individuals homozygous for the rs12101261 disease-associated genotype compared with carriers of the disease-protective allele. Our studies discovered a genetic-epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates escape of TSHR-reactive T cells from central tolerance, triggering GD.
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