Remission of Graves' hyperthyroidism and A/G polymorphism at position 49 in exon 1 of cytotoxic T lymphocyte-associated molecule-4 gene.

Abstract

We studied whether a patient with Graves' disease will go into remission during antithyroid drug (ATD) treatment. Remission of Graves' hyperthyroidism is predicted by a smooth decrease in TSH receptor antibody (TRAb) during ATD treatment. Cytotoxic T cell lymphocyte-associated molecule-4 (CTLA-4) may play an important role in the development of Graves' hyperthyroidism and in its remission. We studied A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene in 144 Japanese Graves' patients. We intended to reveal the possible association of CTLA-4 gene polymorphism with the remission of Graves' hyperthyroidism. All patients with Graves' disease were treated with ATD. Thyroid-stimulating antibody and TSH binding inhibitory Ig were measured as TRAb. We analyzed CTLA-4 genotypes and alleles with PCR. We calculated the frequencies of CTLA-4 genotypes and alleles. A significant increase in the frequency of the G allele was seen in Graves' patients compared with controls (P = 0.0095). Graves' patients were divided into three groups (A, B, and C) according to time of TRAb disappearance after the start of ATD treatment. In group A patients TRAb had disappeared within 1 yr after the start of ATD treatment, in group B TRAb had disappeared between the beginning of the second year and the end of the fifth year of treatment, and in group C TRAb continued to be positive after 5 yr of ATD treatment. The frequencies of the GG genotype and the G allele were significantly higher in group C patients with persistently positive TRAb over 5 yr of ATD treatment than in the other groups (P < 0.0001). Group C patients did not have the AA genotype. The periods of time until remission were significantly shorter in the AA genotype. Graves' patients with the G allele need to continue ATD treatment for longer periods.

• Authors: Yoshino Kinjo, Nobuyuki Takasu, Ichiro Komiya, Takeaki Tomoyose, Masaki Takara, Tsuyoshi Kouki, Yoshinori Shimajiri, Kouichi Yabiku, Hiroshi Yoshimura
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 87 Issue 6 Pg. 2593-6 (Jun 2002) ISSN: 0021-972X [Print] United States
• PMID: 12050220 (Publication Type: Journal Article)

Chemical References

• Antibodies
• Antithyroid Agents
• Receptors, Thyrotropin

Topics

• Adolescent
• Adult
• Aged
• Alleles
• Antibodies (analysis)
• Antithyroid Agents (therapeutic use)
• Exons
• Female
• Gene Frequency
• Genotype
• Graves Disease (drug therapy, genetics, physiopathology)
• Humans
• Male
• Middle Aged
• Polymorphism, Genetic
• Receptors, Thyrotropin (immunology)
• Remission Induction