Yj. Park et al., Polymorphism in the promoter and exon 1 of the cytotoxic T lymphocyte antigen-4 gene associated with autoimmune thyroid disease in Koreans, THYROID, 10(6), 2000, pp. 453-459
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.