Context: Graves' disease (GD) is an autoimmune disorder with genetic predisposition. The thyroglobulin (Tg) is a major autoantigen for GD. The human Tg gene polymorphism has specific features that make it important in GD.

Objective: This study investigated whether Tg SNPs relates to GD development in a Taiwanese population.

Design/Setting:This was a case control association study.

Patients/Outcome Measures: We enrolled 215 Taiwanese patients with GD and 141 controls from the Endocrine Clinic of Kaohsiung Medical University Chung-Ho Memorial Hospital. This study investigated the association between gene polymorphism and relapse of hyperthyroidism after medication was discontinued in three GD patient groups and a control group, compare clinical and laboratory data obtained with patients with the three different genotypes with the three different Tg SNPs (E10SNP158, E12SNP, E33SNP).

Results: We found a significant increase in the T/T genotype of E33SNP compared with the control group (P <0.001). We also found the E33SNP C/C genotype of the Tg gene were strongly associated with a subgroup of GD patients who were also characterized as having a higher relapse rate, significantly higher levels of persisting TSH-receptor antibody at the end of treatment, a higher frequency in smoking and a higher incidence of ophthalmopathy (P <0.05).

Conclusions: This study showed that Taiwanese patients with the C/C genotype of E33SNP, smoking, ophthalmopathy and positive TSH-receptor antibodies at the end of the treatment were more likely to have a relapse of Graves^' hyperthyroidism after antithyroid medication is withdrawn.