Immunologic Research

, Volume 54, Issue 1–3, pp 204–213

Genetic and epigenetic mechanisms in thyroid autoimmunity

Immunology at Mount Sinai


Autoimmune thyroid diseases (AITD), including Graves’ disease and Hashimoto’s thyroiditis, are among the commonest autoimmune disorders, affecting approximately 5 % of the population. Epidemiological data support strong genetic influences on the development of AITD. Since the identification of HLA-DR3 as a major AITD susceptibility gene, there have been significant advances made in our understanding of the genetic mechanisms leading to AITD. We have shown that an amino acid substitution of alanine or glutamine with arginine at position 74 in the HLA-DR peptide binding pocket is a critical factor in the development of AITD, and we are continuing to dissect these mechanisms at the molecular level. In addition to the MHC class II genes, there are now several other confirmed gene loci associated with AITD, including immune-regulatory (CD40, CTLA-4, PTPN22, FOXP3, and CD25) and thyroid-specific genes (thyroglobulin and TSHR). Mechanistically, it is postulated that susceptibility genes interact with certain environmental triggers to induce AITD through epigenetic effects. In this review, we summarize some of the recent advances made in our laboratory dissecting the genetic–epigenetic interactions underlying AITD. As shown in our recent studies, epigenetic modifications offer an attractive mechanistic possibility that can provide further insight into the etiology of AITD.


Thyroid genetics Autoimmune thyroid disorders Epigenetics 

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Division of Endocrinology, Department of MedicineMount Sinai Medical CenterNew YorkUSA
  2. 2.James J. Peters VA Medical CenterBronxUSA

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