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Address correspondence to Dr. Ming-Jiuan Wu, Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan 717, Taiwan, ROC; tel 886 6 266 4911 ext 220; fax 886 6 266 6411; e-mail: imwu{at}mail.chna.edu.tw.
Graves’ disease (GD) is an autoimmune disease but the underlying etiology has not been completely elucidated. Genetic susceptibility has been believed to play a major role. Recent studies showed that the CT60 single nucleotide polymorphism (SNP), which is in the 3'-noncoding region of the CTLA-4 gene, is strongly associated with some immune-mediated diseases. The aim of this study was to test for association between GD susceptibility and polymorphisms of CTLA-4 (ie, the CT60 SNP and the exon 1 +49 SNP) in the Taiwanese population. Our results demonstrate significant differences in the frequencies of the genotypes and alleles between 107 GD patients and 101 control subjects in the CT60 and exon 1 +49 SNPs (p <0.05). Significant differences in phenotypes were only found for CT60 SNP (78.4% vs 67.8% between patients and controls; 
2 = 3.93, p = 0.047). Furthermore, we found that the G/G genotype of both CT60 and exon 1 +49 was associated with increased risk for GD (p = 0.022, OR = 1.97). Significant linkage disequilibrium was found between the CT60 SNP and the exon 1 +49 SNP in both GD patients and control subjects (D’ = 1.00). Because of tight linkage disequilibrium, a combination of these SNPs enhanced the role of the CTLA-4 gene in GD. The frequency of the disease-susceptible G allele of CT60 was comparable to that in Japanese and higher than in Caucasians. In conclusion, we provide evidence that CT60 SNP is associated with susceptibility to GD in the Taiwanese population.
Keywords: CT60 SNP, CTLA-4, exon 1 +49 SNP, Graves’ disease, single nucleotide polymorphism
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