Polymorphism in the promoter and exon 1 of the cytotoxic T lymphocyte antigen-4 gene associated with autoimmune thyroid disease in Koreans

The objective of this study was to examine the polymorphism in the cytotoxi c T lymphocyte antigen-4 (CTLA-4) gene and its relationship with autoimmune thyroid disease in Koreans. Polymorphism in the promoter and exon 1 of CTL A-4 clinical symptoms of disease and thyrotropin receptor antibody (TSHRAb) characteristics were analyzed. Polymorphism was detected using restriction fragment length polymorphism and polymerase chain reaction amplification o f genomic DNA. All subjects were Korean (97 Graves' disease, 110 Hashimoto' s thyroiditis, and 199 normal controls). Graves' patients had significantly more G allele in exon 1 and C allele in the promoter than controls. When t he exon 1 genotype was GG, the frequency of CC genotype in the promoter was higher. Allele frequencies in CTLA-4 did not differ from controls in patie nts with Hashimoto's thyroiditis. In Graves' patients, there were significa nt differences between genotypic groups in serum triiodothyronine (T-3) lev els and the presence of ophthalmopathy. However, TSHRAbs and other clinical characteristics were not significantly different. In conclusion, the CTLA- 4 G allele in exon 1 and C allele in the promoter may confer genetic suscep tibility to Graves' disease in Koreans. These two polymorphisms are additio nal and dependent genetic risk markers that help to characterize risk allel es within CTLA-4 gene.