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.
BACKGROUND
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.


METHODS
This was a case-control association study.


METHODS
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the end of the treatment were more likely to have a relapse of Graves' hyperthyroidism after antithyroid medication is withdrawn.
Hsiao
Jeng-Yueh
JY
Department of Endocrinology and Metabolism, Kaohsiung Medical University Chung-Ho Memorial Hospital, 100 Shin-Chuan 1st Road, Kaohsiung 80761, Taiwan, Republic of China.
Hsieh
Ming-Chia
MC
Tien
Kai-Jen
KJ
Hsu
Shih-Chie
SC
Shin
Shyi-Jang
SJ
Lin
Shiu-Ru
SR
D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics*; D005260:Female; D006111:Graves Disease / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D008713:Methimazole / Q000627:therapeutic use; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011441:Propylthiouracil / Q000627:therapeutic use; D011989:Receptors, Thyrotropin / Q000037:antagonists & inhibitors / Q000276:immunology; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013624:Taiwan; D013954:Thyroglobulin / Q000235:genetics*
D013956:Antithyroid Agents; D011989:Receptors, Thyrotropin; D008713:Methimazole; D011441:Propylthiouracil; D013954:Thyroglobulin