title: Polymorphisms in the cytotoxic T lymphocyte antigen-4 gene region confer susceptibility to Addison's disease.
abstract: The cytotoxic T lymphocyte antigen-4 (CTLA4) gene on chromosome 2q33 encodes a key regulator in the adaptive immune system. The CTLA4 surface molecule is expressed on activated T lymphocytes and involved in down-regulation of the immune response. Previous studies on a possible association between autoimmune Addison's disease and CTLA4 polymorphisms have shown conflicting results. A recent study identified new candidate polymorphisms in the CTLA4 region, influencing gene splicing and thereby the relative abundance of soluble CTLA4. We genotyped 134 patients with Addison's disease and 413 healthy controls from Norway and United Kingdom for these newly identified polymorphisms. Our data demonstrate that the same polymorphisms that have recently been demonstrated to confer susceptibility to autoimmune thyroid disease and type 1 diabetes also confer susceptibility to Addison's disease. This finding suggests that polymorphisms in CTLA4 confer general risk to develop autoimmunity and identifies a potential therapeutic target in the prevention of autoimmune endocrine disorders.
authors.affiliation: Institute of Medical Genetics, University of Oslo, P.O. Box 1036, Blindern, NO-0315 Oslo, Norway. anne.blomhoff@ioks.uio.no
authors.forename: Anne
authors.initials: A
authors.lastname: Blomhoff
authors.forename: Benedicte A
authors.initials: BA
authors.lastname: Lie
authors.forename: Anne G
authors.initials: AG
authors.lastname: Myhre
authors.forename: E Helen
authors.initials: EH
authors.lastname: Kemp
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Weetman
authors.forename: Hanne E
authors.initials: HE
authors.lastname: Akselsen
authors.forename: Eystein S
authors.initials: ES
authors.lastname: Huseby
authors.forename: Dag E
authors.initials: DE
authors.lastname: Undlien
mesh_terms: D000224:Addison Disease / Q000235:genetics*; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D009664:Norway; D011110:Polymorphism, Genetic; D006113:United Kingdom
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers