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A CTLA-4 gene polymorphism is associated with both Graves' disease and autoimmune hypothyroidism

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OBJECTIVEThe autoimmune thyroid diseases, Graves' disease and autoimmune hypothyroidism, result from a complex interaction between genetic, environmental and endogenous factors. The genetic loci conferring susceptibility remain unclear. A recent report has demonstrated an association between a microsatellite polymorphism of the CTLA-4 gene (allele 106) on chromosome 2q33 and Graves' disease in Caucasian patients in the USA. The aim of the present study was to confirm this association in UK patients and to determine whether this polymorphism is also associated with autoimmune hypothyroidism.

DESIGNAnalysis of Caucasian patients with autoimmune thyroid disease from a single clinic, compared to local Caucasian controls.

PATIENTSWe studied 112 patients with Graves' disease, 44 with autoimmune hypothyroidism and 91 controls.

MEASUREMENTSCTLA-4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels.

RESULTSAs in previous studies, 21 alleles of the CTLA-4 microsatellite region were detected. Allele 106 was significantly increased in patients with Graves' disease (P=0.006) and in those with autoimmune hypothyroidism (P=0.02) when compared to controls. There was no significant difference between the groups in the distribution of the other alleles and no association between allele 106 and sex, HLA-DR or -DQ specificities or the presence of ophthalmopathy in the Graves' patients.

CONCLUSIONSThese results confirm that the CTLA-4 gene, or one closely associated with it, confers susceptibility to Grave's disease but is not specific as the CTLA-4 106 allele is also associated with autoimmune hypothyroidism. This association seems to be with autoimmune thyroid disease in general.
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Document Type: Research Article

Affiliations: Department of Medicine, University of Sheffield Clinical Sciences Centre, Sheffield, UK

Publication date: May 1, 1997

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