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 locus 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.
Vaidya
Bijay
B
Department of Diabetes, Endocrinology and Vascular Medicine, Peninsula Medical School, Royal Devon and Exeter Hospital, Exeter EX2 5DW, UK. bvaidya@hgmp.mrc.ac.uk
Pearce
Simon
S
D000224:Addison Disease / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism; D001327:Autoimmune Diseases / Q000235:genetics*; D060908:CTLA-4 Antigen; D002874:Chromosome Mapping; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D004700:Endocrine System Diseases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008213:Lymphocyte Activation; D013601:T-Lymphocytes; D013959:Thyroid Diseases / Q000235:genetics
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human