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Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease.

Publication ,  Journal Article
Ueda, H; Howson, JMM; Esposito, L; Heward, J; Snook, H; Chamberlain, G; Rainbow, DB; Hunter, KMD; Smith, AN; Di Genova, G; Herr, MH; Payne, F ...
Published in: Nature
May 29, 2003

Genes and mechanisms involved in common complex diseases, such as the autoimmune disorders that affect approximately 5% of the population, remain obscure. Here we identify polymorphisms of the cytotoxic T lymphocyte antigen 4 gene (CTLA4)--which encodes a vital negative regulatory molecule of the immune system--as candidates for primary determinants of risk of the common autoimmune disorders Graves' disease, autoimmune hypothyroidism and type 1 diabetes. In humans, disease susceptibility was mapped to a non-coding 6.1 kb 3' region of CTLA4, the common allelic variation of which was correlated with lower messenger RNA levels of the soluble alternative splice form of CTLA4. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain. Genetic mapping of variants conferring a small disease risk can identify pathways in complex disorders, as exemplified by our discovery of inherited, quantitative alterations of CTLA4 contributing to autoimmune tissue destruction.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

May 29, 2003

Volume

423

Issue

6939

Start / End Page

506 / 511

Location

England

Related Subject Headings

  • T-Lymphocytes
  • Protein Isoforms
  • Polymorphism, Single Nucleotide
  • Mice
  • Immunoconjugates
  • Hypothyroidism
  • Humans
  • Graves Disease
  • Genotype
  • Genetic Predisposition to Disease
 

Citation

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Ueda, H., Howson, J. M. M., Esposito, L., Heward, J., Snook, H., Chamberlain, G., … Gough, S. C. L. (2003). Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature, 423(6939), 506–511. https://doi.org/10.1038/nature01621
Ueda, Hironori, Joanna M. M. Howson, Laura Esposito, Joanne Heward, Hywel Snook, Giselle Chamberlain, Daniel B. Rainbow, et al. “Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease.Nature 423, no. 6939 (May 29, 2003): 506–11. https://doi.org/10.1038/nature01621.
Ueda H, Howson JMM, Esposito L, Heward J, Snook H, Chamberlain G, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003 May 29;423(6939):506–11.
Ueda, Hironori, et al. “Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease.Nature, vol. 423, no. 6939, May 2003, pp. 506–11. Pubmed, doi:10.1038/nature01621.
Ueda H, Howson JMM, Esposito L, Heward J, Snook H, Chamberlain G, Rainbow DB, Hunter KMD, Smith AN, Di Genova G, Herr MH, Dahlman I, Payne F, Smyth D, Lowe C, Twells RCJ, Howlett S, Healy B, Nutland S, Rance HE, Everett V, Smink LJ, Lam AC, Cordell HJ, Walker NM, Bordin C, Hulme J, Motzo C, Cucca F, Hess JF, Metzker ML, Rogers J, Gregory S, Allahabadia A, Nithiyananthan R, Tuomilehto-Wolf E, Tuomilehto J, Bingley P, Gillespie KM, Undlien DE, Rønningen KS, Guja C, Ionescu-Tîrgovişte C, Savage DA, Maxwell AP, Carson DJ, Patterson CC, Franklyn JA, Clayton DG, Peterson LB, Wicker LS, Todd JA, Gough SCL. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature. 2003 May 29;423(6939):506–511.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

May 29, 2003

Volume

423

Issue

6939

Start / End Page

506 / 511

Location

England

Related Subject Headings

  • T-Lymphocytes
  • Protein Isoforms
  • Polymorphism, Single Nucleotide
  • Mice
  • Immunoconjugates
  • Hypothyroidism
  • Humans
  • Graves Disease
  • Genotype
  • Genetic Predisposition to Disease