This study investigates whether Tg gene polymorphisms can be associated with Graves' disease (GD) in a Taiwanese population and identifies potential polygenic susceptive genes for GD. The findings of such a study may have important implications for prognostic prediction and treatment of GD. We performed case control association studies for the 3 discovered Tg single nucleotide polymorphisms (SNPs) (E10, E12, E33) in 215 GD patients and 141 controls. The three SNPs were identified within the Tg gene. These SNPs were analysed by a fluorescent-based restriction fragment length polymorphism method (RFLP) and PCR. The genotype and allele frequencies at E10SNP158, E12SNP and E33SNP in GD patients were compared with those of the controls. In addition, we analysed the interactions between these SNPs and the clinical and laboratory variables. We found a significant difference in the T/T genotype of E33SNP and G/G genotype of E12SNP compared with the control group (p<0.001). We also found the E33SNP T/T genotype to be positively associated with development of GD, whereas the E12SNP G/G genotype protected it.