Remission of Graves' hyperthyroidism and A/G polymorphism at position 49 in exon 1 of cytotoxic T lymphocyte-associated molecule-4 gene.
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.
Kinjo
Yoshino
Y
Second Department of Internal Medicine, School of Medicine, University of the Ryukyus, Uehara 207, Nishihara, Okinawa 902-0215, Japan. pm7500@dns.2naidomon.naha.okinawa.jp
Takasu
Nobuyuki
N
Komiya
Ichiro
I
Tomoyose
Takeaki
T
Takara
Masaki
M
Kouki
Tsuyoshi
T
Shimajiri
Yoshinori
Y
Yabiku
Kouichi
K
Yoshimura
Hiroshi
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000906:Antibodies / Q000032:analysis; D013956:Antithyroid Agents / Q000627:therapeutic use*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006111:Graves Disease / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011989:Receptors, Thyrotropin / Q000276:immunology; D012074:Remission Induction
D000906:Antibodies; D013956:Antithyroid Agents; D011989:Receptors, Thyrotropin