The Genetics of Autoimmune Thyroid Disease

Recent studies have confirmed that polymorphisms in several genes confer susceptibility for the development of autoimmune thyroid disease, and that of these HLA-DR alleles, and the genes encoding CTLA-4, PTPN22, FCRL3, and probably the IL-2 receptor all have associations with other autoimmune disorders, indicating that they provide a lowering of the background threshold for the development of autoimmunity. Other factors (the TSHR and possibly Tg genes, HLA-C alleles, and environmental factors) determine that the type of disease which results from this background propensity specifically targets the thyroid. We also now appreciate much better how complex these disorders are in their pathogenesis: multiple genes influencing multiple immunological pathways are involved in pathogenesis, but are not involved in every patient. Any individual patient with thyroid autoimmunity has their own cluster of genetic (and environmental) susceptibility factors, only very partially shared with other patients who have the same diagnostic and clinical label. The interplay of forces that cause autoimmune thyroid disease in an individual patient are more subtle than previously imagined and there is at present no obvious upper limit on the number of genes which may be involved.