Association between the Severity of Hashimoto's Disease and the Functional +874A/T Polymorphism in the Interferon-.GAMMA. Gene

Abstract

Abstract. CD8 + CD25 + -activated cytotoxic T cells and anti-thyroglobulin antibodies (TgAb) are independently involved in the severity of Hashimoto's disease (HD). Interferon γ (IFN-γ) activates cytotoxic T cells. To evaluate the hypothesis that the functional +874A/T polymorphism in the gene encoding IFN-γ 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-γ 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-γ gene is associated with severity of HD.

Functional polymorphisms affecting Th1 differentiation are associated with the severity of autoimmune thyroid diseases

“…We previously reported that a high genetic expression of IFN-γ and a high proportion of Th1 cells were associated with the severity of HD [8,10]. IL-18 enhanced the production of Th1 cytokines, such as IFN-γ [22,23].…”

“…Th1 cells mainly produce interferon (IFN)-γ that promotes cell-mediated immunity [1,3,4]. We previously reported that CD8 + CD25 + activated cytotoxic T cells and Th1 cells were increased in patients with severe HD [8,9] and that higher production of IFN-γ was more frequent in patients with severe HD than in those with mild HD [10]. Moreover, lower expression of T-box 21 (TBX21), the master transcription factor of Th1 cells, was associated with intractability of GD [11].…”

The association between severity of obstructive sleep apnea and prevalence of Hashimoto’s thyroiditis

“…IFN-γ, TNF-α) were shown to play a crucial role in the pathogenesis and severity of autoimmune thyroid diseases [7][8][9][10]. However, the trigger of the induction has not been well understood.…”

The −590CC Genotype in the IL4 Gene as a Strong Predictive Factor for the Development of Hypothyroidism in Hashimoto Disease

“…Likewise, the intractability of Graves disease (GD) is difficult to predict. Autoimmune thyroid destruction that underlies both diseases is strongly determined by T-cell cytotoxicity, which is activated by interferon (IFN)-␥ (1 ), and the T allele in ϩ874A/T polymorphism of the interferon gamma (IFNG) gene, which promotes increased IFN-␥ production, has been noted more frequently among patients with severe HD (2 ). Cytokine balance between T-helper 1 (Th1) cytokines, such as IFN-␥, and Th2 cytokines is important in immune regulation (3 ).…”