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

General

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.
RGD ID:	7421505
Pubmed:	PMID:12780750 (View Abstract at PubMed)
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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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Graves' disease	susceptibility	IAGP		7421505	DNA:SNPs:exon more ...	RGD
Graves' disease	susceptibility	ISO	CTLA4 (Homo sapiens)	7421505; 7421505	DNA:SNPs:exon more ...	RGD

Objects Annotated

Genes (Rattus norvegicus)

Ctla4 (cytotoxic T-lymphocyte-associated protein 4)

Genes (Mus musculus)

Ctla4 (cytotoxic T-lymphocyte-associated protein 4)

Genes (Homo sapiens)

CTLA4 (cytotoxic T-lymphocyte associated protein 4)

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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.