Genetics of Thyroid Disorders

Thyroid diseases are the most common endocrine pathologies second to diabetes. They have been shown to have high genetic impact, and variants in any of the genes involved in the metabolism of thyroid hormones have marked influence on the development of these diseases.

To identify the genes that have been most involved in the development of thyroid pathologies by reviewing the literature with recent relevant articles.

We performed a literature search on the NCBI (National Center for Biotechnology Information) databases, and that of the European Bioinformatics Institute (EMBL-EBI) using keywords related to the topic of interest).

Activation of oncogenes such as RAS, BRAF, RET/PTC and the overstimulation of the PI3K/AKT pathway plays an important role in thyroid tumorigenesis. SLC5A5, SLC26A4, TG, TPO, DUOX2, DUOXA2 are related to hypothyroidism. Risk factors for Graves' disease are associated with the presence of HLA-DR3, CTLA4, PTPN22, CD40, IL2RA (CD25), FCRL3, and IL23R. FOXE1 can be associated to hypothyroidism and papillary thyroid cancer.

Thyroid diseases are polygenetic, and while there are sufficient pathways affected by genetic changes, and there is, to our knowledge, no gene that has been found to be specifically causal, and the pathology has been the result of the interaction of many genetic variables such as polymorphisms or mutations.