TPO

The TPO gene provides instructions for making an enzyme called thyroid peroxidase. This enzyme plays a central role in the function of the thyroid gland, a butterfly-shaped tissue in the lower neck. Thyroid peroxidase assists the chemical reaction that adds iodine to a protein called thyroglobulin, a critical step in generating thyroid hormones. Thyroid hormones play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism).

To function properly, thyroid peroxidase must be located in the cell membrane of certain thyroid cells, called follicular cells. Thyroid peroxidase has several different versions (isoforms), which vary by size and location within the cell. Some versions are inactive because they are not located in the cell membrane.

congenital hypothyroidism - caused by mutations in the TPO gene

Researchers have identified more than 30 TPO gene mutations that delete, add, or change DNA building blocks (base pairs) in the TPO gene. Some mutations lead to an abnormally small thyroid peroxidase enzyme that breaks apart before it can be inserted into the cell membrane. Other mutations change the enzyme's 3-dimensional shape, preventing it from functioning properly within the cell membrane. Without functional thyroid peroxidase, iodine taken up by the thyroid gland is not added to thyroglobulin. As a result, the production of thyroid hormones is absent or reduced, leading to the features of congenital hypothyroidism. In most affected individuals, the thyroid gland is enlarged (goiter) in an attempt to compensate for reduced hormone production.

autoimmune disorders - associated with the TPO gene

A major cause of thyroid disease is autoimmunity, in which the body's immune response turns against itself. The autoimmune response is triggered by a combination of genetic and environmental factors and involves the production of large Y-shaped proteins called antibodies or immunoglobulins. Instead of attacking foreign substances such as toxins or proteins from bacteria and viruses, these antibodies inappropriately attack thyroid proteins. Antibodies that attack the body's own proteins are called autoantibodies. The presence of autoantibodies to thyroid peroxidase is an indication of autoimmune thyroid disease.

The two most common thyroid autoimmune diseases are Graves disease and Hashimoto thyroiditis. Abnormal levels of thyroid hormones and an enlarged thyroid gland (goiter) are features of these disorders. Autoantibodies to thyroid peroxidase are present in about 75 percent of people with Graves disease and 90 percent of those with Hashimoto thyroiditis.