title: The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry.
abstract: Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell-mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ-specific autoimmune disease.
authors.affiliation: Istituto Clinica Medica II, University of Rome La Sapienza, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Nisticò
authors.forename: R
authors.initials: R
authors.lastname: Buzzetti
authors.forename: L E
authors.initials: LE
authors.lastname: Pritchard
authors.forename: B
authors.initials: B
authors.lastname: Van der Auwera
authors.forename: C
authors.initials: C
authors.lastname: Giovannini
authors.forename: E
authors.initials: E
authors.lastname: Bosi
authors.forename: M T
authors.initials: MT
authors.lastname: Larrad
authors.forename: M S
authors.initials: MS
authors.lastname: Rios
authors.forename: C C
authors.initials: CC
authors.lastname: Chow
authors.forename: C S
authors.initials: CS
authors.lastname: Cockram
authors.forename: K
authors.initials: K
authors.lastname: Jacobs
authors.forename: C
authors.initials: C
authors.lastname: Mijovic
authors.forename: S C
authors.initials: SC
authors.lastname: Bain
authors.forename: A H
authors.initials: AH
authors.lastname: Barnett
authors.forename: C L
authors.initials: CL
authors.lastname: Vandewalle
authors.forename: F
authors.initials: F
authors.lastname: Schuit
authors.forename: F K
authors.initials: FK
authors.lastname: Gorus
authors.forename: R
authors.initials: R
authors.lastname: Tosi
authors.forename: P
authors.initials: P
authors.lastname: Pozzilli
authors.forename: J A
authors.initials: JA
authors.lastname: Todd
mesh_terms: D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics; D006801:Humans; D018796:Immunoconjugates; D009679:Nuclear Family; D017354:Point Mutation; D011110:Polymorphism, Genetic
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept