Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis

From epidemiology to mechanisms

Amanda Huber, Francesca Menconi, Sarah Corathers, Eric M. Jacobson, Yaron Tomer

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Type 1 diabetes (T1D) and autoimmune thyroid diseases (AITD) frequently occur together within families and in the same individual. The co-occurrence of T1D and AITD in the same patient is one of the variants of the autoimmune polyglandular syndrome type 3 [APS3 variant (APS3v)]. Epidemiological data point to a strong genetic influence on the shared susceptibility to T1D and AITD. Recently, significant progress has been made in our understanding of the genetic association between T1D and AITD. At least three genes have been confirmed as major joint susceptibility genes for T1D and AITD: human leukocyte antigen class II, cytotoxic T-lym-phocyte antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22. Moreover, the first whole genome linkage study has been recently completed, and additional genes will soon be identified. Not unexpectedly, all the joint genes for T1D and AITD identified so far are involved in immune regulation, specifically in the presentation of antigenic pep-tides to T cells. One of the lessons learned from the analysis of the joint susceptibility genes for T1D and AITD is that subset analysis is a key to dissecting the etiology of complex diseases. One of the best demonstrations of the power of subset analysis is the CTLA-4 gene in T1D. Although CTLA-4 showed very weak association with T1D, when analyzed in the subset of patients with both T1D and AITD, the genetic effect of CTLA-4 was significantly stronger. Gene-gene and genetic-epigenetic interactions most likely play a role in the shared genetic susceptibility to T1D and AITD. Dissecting these mechanisms will lead to a better understanding of the etiology of T1P and AITD, as well as autoimmunity in general.

Original languageEnglish (US)
Pages (from-to)697-725
Number of pages29
JournalEndocrine Reviews
Volume29
Issue number6
DOIs
StatePublished - Oct 2008
Externally publishedYes

Fingerprint

Autoimmune Thyroiditis
Genetic Predisposition to Disease
Thyroid Diseases
Type 1 Diabetes Mellitus
Autoimmune Diseases
Epidemiology
Joints
Genes
Antigens
Non-Receptor Type 4 Protein Tyrosine Phosphatase
Non-Receptor Type 22 Protein Tyrosine Phosphatase
Autoimmune Polyendocrinopathies
HLA Antigens
Autoimmunity
Epigenomics

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis : From epidemiology to mechanisms. / Huber, Amanda; Menconi, Francesca; Corathers, Sarah; Jacobson, Eric M.; Tomer, Yaron.

In: Endocrine Reviews, Vol. 29, No. 6, 10.2008, p. 697-725.

Research output: Contribution to journalArticle

Huber, Amanda ; Menconi, Francesca ; Corathers, Sarah ; Jacobson, Eric M. ; Tomer, Yaron. / Joint genetic susceptibility to type 1 diabetes and autoimmune thyroiditis : From epidemiology to mechanisms. In: Endocrine Reviews. 2008 ; Vol. 29, No. 6. pp. 697-725.
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