Genetics and epigenetics of autoimmune thyroid diseases: Translational implications

Best Pract Res Clin Endocrinol Metab. 2023 Mar;37(2):101661. doi: 10.1016/j.beem.2022.101661. Epub 2022 Apr 11.

Abstract

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are prevalent autoimmune disorders, representing opposite ends of the clinical spectrum of autoimmune thyroid diseases (AITD). The pathogenesis involves a complex interplay between environment and genes. Specific susceptibility genes have been discovered that predispose to AITD, including thyroid-specific and immune-regulatory genes. Growing evidence has revealed that genetic and epigenetic variants can alter autoantigen presentation during the development of immune tolerance, can enhance self-peptide binding to MHC (major histocompatibility complex), and can amplify stimulation of T- and B-cells. These gene-driven mechanistic discoveries lay the groundwork for novel treatment targets. This review summarizes recent advances in our understanding of key AITD susceptibility genes (Tg1, TSHR, HLA-DR3, and CD40) and their translational therapeutic potential.

Keywords: CD40; HLA; TSHR; autoimmune thyroid disease; genes; thyroglobulin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Autoimmune Diseases* / complications
  • Epigenesis, Genetic
  • Genetic Predisposition to Disease
  • Graves Disease*
  • Hashimoto Disease* / complications
  • Hashimoto Disease* / genetics
  • Humans
  • Thyroid Diseases* / complications