Genetic and epigenetic mechanisms in thyroid autoimmunity

Alia Hasham, Yaron Tomer

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)204-213
Number of pages10
JournalImmunologic Research
Volume54
Issue number1-3
DOIs
StatePublished - Dec 2012

Fingerprint

Thyroid Diseases
Autoimmunity
Epigenomics
Autoimmune Diseases
Thyroid Gland
Genes
HLA-DR3 Antigen
Hashimoto Disease
MHC Class II Genes
Thyroglobulin
Graves Disease
Disease Susceptibility
HLA-DR Antigens
Amino Acid Substitution
Glutamine
Alanine
Arginine
Peptides

Keywords

  • Autoimmune thyroid disorders
  • Epigenetics
  • Thyroid genetics

ASJC Scopus subject areas

  • Immunology

Cite this

Genetic and epigenetic mechanisms in thyroid autoimmunity. / Hasham, Alia; Tomer, Yaron.

In: Immunologic Research, Vol. 54, No. 1-3, 12.2012, p. 204-213.

Research output: Contribution to journalArticle

@article{842f8954f05d4cee92720c20f98d64ac,
title = "Genetic and epigenetic mechanisms in thyroid autoimmunity",
abstract = "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.",
keywords = "Autoimmune thyroid disorders, Epigenetics, Thyroid genetics",
author = "Alia Hasham and Yaron Tomer",
year = "2012",
month = "12",
doi = "10.1007/s12026-012-8302-x",
language = "English (US)",
volume = "54",
pages = "204--213",
journal = "Immunologic Research",
issn = "0257-277X",
publisher = "Humana Press",
number = "1-3",

}

TY - JOUR

T1 - Genetic and epigenetic mechanisms in thyroid autoimmunity

AU - Hasham, Alia

AU - Tomer, Yaron

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

KW - Autoimmune thyroid disorders

KW - Epigenetics

KW - Thyroid genetics

UR - http://www.scopus.com/inward/record.url?scp=84867853690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867853690&partnerID=8YFLogxK

U2 - 10.1007/s12026-012-8302-x

DO - 10.1007/s12026-012-8302-x

M3 - Article

VL - 54

SP - 204

EP - 213

JO - Immunologic Research

JF - Immunologic Research

SN - 0257-277X

IS - 1-3

ER -