The Genetics of Autoimmune Thyroid Disease

Autoimmune thyroid diseases (AITD), e.g. Graves' hyperthyroidism, are prototypes of common human disorders in which multiple genes as well as environmental factors are involved. Some genes important in their pathogenesis are probably shared between these diseases (also with non-endocrine autoimmune diseases, e.g. autoimmune gastritis), whereas others might be disease specific. Population-based association studies have consistently identified alleles in the major histocompatibility complex (MHC) and CTLA4 as conferring risks for AITD. Genetic linkage and genome scan studies have identified over 20 potential loci. Only one, however, has been convincingly replicated and maps at 5q31. In spite of its recent emergence as a gatekeeper gene for autoimmunity, linkage of CLTA4 to AITD was described only in one subset of a UK population. Like many other complex genetic disorders, teasing out the genes involved in the pathogenesis of AITD is limited by the ability of current methods of data analysis to discern the influence of genes of minor effect in a relatively small database. © 2003, by Walter de Gruyter GmbH & Co. All rights reserved.