Searching for the Autoimmune Thyroid Disease Susceptibility Genes: From Gene Mapping to Gene Function
Yaron Tomer and
Terry F. Davies
Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029
Correspondence: Address all correspondence and requests for reprints to: Yaron Tomer, M.D., Division of Endocrinology, Diabetes and Bone Diseases, Box 1055, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, New York 10029. E-mail: Yaron.Tomer{at}mssm.edu
The autoimmune thyroid diseases (AITD) are complex diseasesthat are caused by an interaction between susceptibility genesand environmental triggers. Genetic susceptibility, in combinationwith external factors (e.g., dietary iodine), is believed toinitiate the autoimmune response to thyroid antigens. Abundantepidemiological data, including family and twin studies, pointto a strong genetic influence on the development of AITD. Varioustechniques have been used to identify the genes contributingto the etiology of AITD, including candidate gene analysis andwhole genome screening. These studies have enabled the identificationof several loci (genetic regions) that are linked with AITD,and in some of these loci putative AITD susceptibility geneshave been identified. Some of these genes/loci are unique toGraves’ disease (GD) and Hashimoto’s thyroiditis(HT), and some are common to both diseases, indicating thatthere is a shared genetic susceptibility to GD and HT. The putativeGD and HT susceptibility genes include both immune modifyinggenes (e.g., human leukocyte antigen, cytotoxic T lymphocyteantigen-4) and thyroid-specific genes (e.g., TSH receptor, thyroglobulin).Most likely these loci interact, and their interactions mayinfluence disease phenotype and severity. It is hoped that inthe near future additional AITD susceptibility genes will beidentified and the mechanisms by which they induce AITD willbe unraveled.
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