TSH Receptor Gene and Autoimmune Thyroid Diseases
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Abstract
The primary regulators of thyroid activity are the thyroid-stimulating hormone (TSH) and its receptor (TSH-R). Studies have shown that genetic variants in the TSHR gene can increase susceptibility to autoimmune thyroid diseases (AITD). The TSHR gene is located on chromosome 14q31 and encodes a membrane-bound receptor that interacts with TSH to regulate thyroid hormone synthesis and secretion. AITD including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are the most common thyroid disorders, affecting millions of people worldwide. In AITD, autoantibodies can bind to and activate the TSHR, leading to increased thyroid hormone production and secretion in GD, or thyroid destruction and hypothyroidism in HT. In addition to its role in thyroid hormone synthesis and secretion, some studies also revealed that the TSHR has also been implicated in a variety of other physiological processes, including bone metabolism, reproduction, and immune regulation. Genetic variation in the TSHR region may affect the expression, post-translational processing, and/or protein structure, which in turn may cause or worsen the autoimmune response. The TSHR gene and its products are widely used in diagnostic testing for AITD. Understanding the molecular mechanisms underlying the interaction between the TSHR and autoantibodies is critical for developing new diagnostic and therapeutic strategies for AITD.
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