Risk factor and impact on Graves disease: Genetic history

Graves' disease, an autoimmune thyroid disorder characterized by the overproduction of thyroid hormones, can be influenced by various risk factors, with genetics or family history playing a pivotal role in increasing susceptibility to this condition (Antonelli et al., 2020). Firstly, individuals with a family history of autoimmune thyroid diseases, including Graves' disease, may inherit susceptibility genes linked to these disorders. These genes often encode specific proteins involved in immune regulation and thyroid function (Abd Ellatif et al., 2018). When these genes are passed down through generations, there is a higher likelihood that the immune system of affected individuals may have an altered response to thyroid-related antigens. Consequently, the immune system may become more prone to mounting an autoimmune attack against the thyroid gland (Davies et al., 2020). An autoimmune reaction in which the body's immune system wrongly targets the thyroid gland underlies the pathophysiology behind Graves' disease. By affecting how well the immune system can distinguish among self and non-self antigens, genetic variables can have a big impact on this process (Simmonds & Gough, 2018). The immune system may become weakened in people with a genetic susceptibility, which could cause thyroid proteins to be mistaken for foreign entities. An autoimmune cascade that targets the thyroid gland is set off by this misidentification (Davies et al., 2020).

Additionally, thyroid-stimulating immunoglobulins (TSIs) can produce and function differently depending on hereditary variables. By attaching to and turning on the TSH receptors on thyroid cells, these autoantibodies imitate the effects of thyroid-stimulating hormone (TSH) (Morshed et al., 2018). Genetic variations may impact the composition and mechanism of action of TSIs, increasing their potency in activating the thyroid gland. The thyroid gland may experience a stronger and longer stimulation in people with particular genetic variations, which could lead to an excessive amount of thyroid hormone production and release (Davies et al., 2020). Additionally, genes involved in thyroid function can affect how active the thyroid is generally. Variations in the genes that control the synthesis and regulation of thyroid hormone can cause basic thyroid hormone levels to be greater than normal or cause the thyroid hormone to react to autoimmune attacks differently (Bogusławska et al., 2022). Thus, Graves' illness is a complicated interplay between genetic vulnerability and environmental triggers, and these genetic variants can influence the severity and course of the condition in affected individuals.

References

Abd Ellatif, M., Musalam, A. O., El-Gamal, B., & Malik, A. (2018). The Genetic Etiology of Autoimmune Thyroid Diseases: The Neverending Story. CPQ Medicine2(1). https://www.cientperiodique.com/article/CPQME-2-1-5.pdf

Antonelli, A., Ferrari, S. M., Ragusa, F., Elia, G., Paparo, S. R., Ruffilli, I., & Fallahi, P. (2020). Graves’ disease: Epidemiology, genetic and environmental risk factors and viruses. Best Practice & Research Clinical Endocrinology & Metabolism34(1), 101387. https://doi.org/10.1016/j.beem.2020.101387

Bogusławska, J., Godlewska, M., Gajda, E., & Piekiełko-Witkowska, A. (2022). Cellular and molecular basis of thyroid autoimmunity. European Thyroid Journal11(1). https://doi.org/10.1530/ETJ-21-0024

Davies, T. F., Andersen, S., Latif, R., Nagayama, Y., Barbesino, G., Brito, M., & Kahaly, G. J. (2020). Graves’ disease. Nature Reviews Disease Primers6(1), 52. https://doi.org/10.1038/s41572-020-0184-y

Davies, T. F., Andersen, S., Latif, R., Nagayama, Y., Barbesino, G., Brito, M., & Kahaly, G. J. (2020). Graves’ disease (Primer). Nature Reviews: Disease Primers6(1). https://doi.org/10.1038/s41572-020-0184-y

Morshed, S. A., Ma, R., Latif, R., & Davies, T. F. (2018). Biased signaling by thyroid-stimulating hormone receptor–specific antibodies determines thyrocyte survival in autoimmunity. Science Signaling11(514), eaah4120. https://doi.org/10.1126/scisignal.aah41

Simmonds, M., & Gough, S. (2018). Autoimmunity and the Endocrine System. http://eprints.lincoln.ac.uk.pdf

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