title: Genetics of thyroid autoimmunity and the role of the TSHR.
abstract: Graves' disease (GD) and Hashimoto's thyroiditis (HT) make up the autoimmune thyroid diseases (AITD), with classical clinical characteristics arising as a result of environmental factors in people who are genetically predisposed. Three gene regions consistently associated with AITD include the Human Leucocyte Antigen (HLA) region, CTLA4 and PTPN22, which represent general autoimmune risk loci and encode molecules vital for correct immune system function. AITD patients in addition are likely to carry at least one thyroid specific susceptibility locus. Recent genetic studies have refined association of the TSHR with GD to within a 40kb region including intron 1, of the TSHR itself, with preliminary evidence to suggest altered mRNA isoform expression. These findings, combined with previous functional data demonstrating that the TSHR A-subunit is the primary autoantigenic region, suggests novel mechanisms for the onset of GD and a potential therapeutic target.
authors.affiliation: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, UK. o.j.brand@bham.c.uk
authors.forename: O J
authors.initials: OJ
authors.lastname: Brand
authors.forename: S C L
authors.initials: SC
authors.lastname: Gough
mesh_terms: D015551:Autoimmunity / Q000235:genetics; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D050031:Hashimoto Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000276:immunology; D011989:Receptors, Thyrotropin / Q000235:genetics* / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D011989:Receptors, Thyrotropin; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22