The emerging role of the CTLA-4 gene in autoimmune endocrinopathies

It is thought that the majority of autoimmune endocrinopathies, including Graves' disease, autoimmune hypothyroidism, type 1 diabetes mellitus and autoimmune Addison's disease (sporadic and as well as autoimmune polyendocrinopathy syndrome type 2) are inherited as complex genetic traits. Multiple genetic and environmental factors interact with each other to confer susceptibility to these disorders. In recent years there have been considerable efforts towards defining susceptibility genes for complex traits. These investigations have shown, with increasing evidence, that the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene is an important susceptibility focus for autoimmune endocrinopathies and other autoimmune disorders. Here we review the genetic and functional analyses of the CTLA-4 locus in autoimmune endocrinopathies, and discuss the recent efforts in fine-mapping this locus.