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CTLA4 gene and Graves' disease: association of Graves' disease with the CTLA4 exon 1 and intron 1 polymorphisms, but not with the promoter polymorphism.

Authors: Vaidya, B  Oakes, EJ  Imrie, H  Dickinson, AJ  Perros, P  Kendall-Taylor, P  Pearce, SH 
Citation: Vaidya B, etal., Clin Endocrinol (Oxf). 2003 Jun;58(6):732-5.
Pubmed: (View Article at PubMed) PMID:12780750

OBJECTIVE: Recent studies have shown that Graves' disease (GD) is linked to and associated with alleles of the cytotoxic T lymphocyte antigen-4 (CTLA4) locus. However, the true pathogenic polymorphism(s) at this locus remains uncertain. Moreover, the association studies of the promoter CTLA4(-318)C/T polymorphism in white GD populations have produced conflicting results. Therefore, we have analysed three CTLA4 single nucleotide polymorphisms, including promoter CTLA4(-318)C/T, exon 1 CTLA4(49)A/G and intron 1 CTLA4(1822)C/T in our GD cohort from the UK. PATIENTS AND METHODS: We studied 301 white patients with GD and 349 healthy ethnically matched local controls. Amongst GD probands, 129 had significant thyroid-associated orbitopathy (TAO; NOSPECS class III or worse). The CTLA4(-318)C/T, CTLA4(49)A/G and CTLA4(1822)C/T polymorphisms were genotyped by using the restriction enzymes MseI, Bst71I and HaeIII, respectively. RESULTS: We found no association between GD and alleles of CTLA4(-318)C/T. GD was found to be associated with the G allele of CTLA4(49)A/G[P = 5.9 x 10(-6), odds ratio (OR) 1.65] and the T allele of CTLA4(1822)C/T (P = 7.7 x 10(-6), OR 1.64). The frequencies of these alleles were significantly higher in GD probands with significant TAO than in those without TAO (G allele: P = 0.001, OR 1.68; T allele: P = 0.001, OR 1.70). CONCLUSIONS: The promoter CTLA4(-318)C/T polymorphism is not in linkage disequilibrium with the pathogenic polymorphism(s) at the CTLA4 locus. The alleles of both the exon 1 CTLA4(49)A/G and the intron 1 CTLA4(1822)C/T polymorphisms are associated with GD, which is stronger in patients with TAO.

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RGD Object Information
RGD ID: 7421505
Created: 2013-11-20
Species: All species
Last Modified: 2013-11-20
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.