Association between a C/T polymorphism in Exon 33 of the thyroglobulin gene is associated with relapse of graves' hyperthyroidism after antithyroid withdrawal in Taiwanese

作者:Hsiao Jeng Yueh; Hsieh Ming Chia; Tien Kai Jen; Hsu Shih Chie; Shin Shyi Jang; Lin Shiu Ru*
来源:Journal of Clinical Endocrinology & Metabolism, 2007, 92(8): 3197-3201.
DOI:10.1210/jc.2007-0675

摘要

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 single nucleotide polymorphisms (SNPs) relate to GD development in a Taiwanese population. Design and Setting: This was a case-control association study. Patients and Main 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. We also compared clinical and laboratory data obtained from patients with the three different genotypes with the three different Tg SNPs (E10SNP158, E12SNP, and 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 was 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the end of the treatment were more likely to have a relapse of Graves' hyperthyroidism after antithyroid medication is withdrawn.