Association between the severity of Hashimoto's disease and the functional +874A/T polymorphism in the interferon-gamma gene.
CD8+ CD25+-activated cytotoxic T cells and anti-thyroglobulin antibodies (TgAb) are independently involved in the severity of Hashimoto's disease (HD). Interferon gamma (IFN-gamma) activates cytotoxic T cells. To evaluate the hypothesis that the functional +874A/T polymorphism in the gene encoding IFN-gamma is associated with the severity of HD, we examined the frequencies of this polymorphism in 34 HD patients who developed hypothyroidism (severe HD); 22 untreated, euthyroid HD patients (mild HD); 49 patients with intractable Graves' disease (GD); 16 GD patients in remission; and 57 healthy volunteers. Frequency of the +874T allele, which is associated with high IFN-gamma production, was higher in patients with severe HD than in those with mild HD (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.0-12.4; p = 0.047), but there was no difference in the frequency between GD patients. The difference in the frequency of +874T was observed in the subset of patients with HD negative for TgAb (OR, 8.4; 95% CI, 1.2-57.3; p = 0.029) but not in the subset of patients with HD positive for TgAb. Our data indicate that the +874A/T polymorphism in the IFN-gamma gene is associated with severity of HD.
Ito
Chisato
C
Department of Biomedical Informatics, Division of Health Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Watanabe
Mikio
M
Okuda
Noriko
N
Watanabe
Chikami
C
Iwatani
Yoshinori
Y
D001323:Autoantibodies / Q000097:blood; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D005838:Genotype; D006111:Graves Disease / Q000097:blood / Q000235:genetics / Q000276:immunology; D050031:Hashimoto Disease / Q000097:blood / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018709:Statistics, Nonparametric; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; C006606:anti-thyroglobulin; C094372:thyrotropin-binding inhibitory immunoglobulin; D014284:Triiodothyronine; D007371:Interferon-gamma; D013972:Thyrotropin; D004247:DNA; D013974:Thyroxine