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Epidemiology and Genetic Factors in Graves’ Disease and Graves’ Ophthalmopathy

  • Chapter
Graves' Disease

Abstract

Graves’ disease (GD) is an organ-specific autoimmune disease, characterized by the production of antibodies to the TSH receptor that bind to the TSH receptor activating it and resulting in the clinical manifestations of hyperthyroidism. One of the most serious complications of GD is Graves’ ophthalmopathy (GO), a complex chronic autoimmune inflammation affecting the orbital and retro-orbital tissues. Epidemiological studies and sibling and twin studies provide convincing evidence for genetic involvement in the etiology of GD. Earlier genetic studies have primarily focused on the major histocompatibility complex class II as a main genetic factor involved in the development of GD and GO; however, other immune regulatory genes have been shown to be involved in GD. The change of focus on other immune regulatory genes such as CTLA-4, PTPN22, CD40, CD25, and FOXP3 has brought new insights into disease development. Our group and others have further focused on thyroid-specific genes such as TSH receptor and thyroglobulin gene and have shown that they play a major role in GD. Genetic studies in GO, however, did not show consistent results. Since the entire risk for GD is not conveyed by genetic susceptibility alone, it is clear that environmental factors and epigenetic modifications are necessary for the development of GD. Several environmental triggers such as iodine excess, infection, smoking, and medications (e.g., interferon-α) have been clearly shown to contribute to the development of GD, while smoking and radioiodine are the major nongenetic risk factors for GO.

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The authors have no potential conflicts of interest to declare.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, Mount Sinai School of Medicine at Mount Sinai, One Gustav L. Levy Place, Box 1055, New York, NY, 10029, USA

    Sara Salehi Hammerstad M.D., Ph.D.

  2. Division of Pediatric Endocrinology and Diabetes, Oslo University Hospital—Ullevål, 4950, Oslo, 0424, Norway

    Sara Salehi Hammerstad M.D., Ph.D.

  3. James J. Peters VA Medical Center, Bronx, NY, USA

    Yaron Tomer M.D.

  4. Division of Endocrinology, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1055, New York, NY, 10029, USA

    Yaron Tomer M.D.

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  1. Sara Salehi Hammerstad M.D., Ph.D.
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  2. Yaron Tomer M.D.
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Correspondence to Yaron Tomer M.D. .

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  1. Mayo Clinic College of Medicine, Division of Endocrinology and Metabolism, Mayo Clinic, Rochester, Minnesota, USA

    Rebecca S. Bahn

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Hammerstad, S.S., Tomer, Y. (2015). Epidemiology and Genetic Factors in Graves’ Disease and Graves’ Ophthalmopathy. In: Bahn, R. (eds) Graves' Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2534-6_3

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