Involvement of functional polymorphisms in the TNFA gene in the pathogenesis of autoimmune thyroid diseases and production of anti-thyrotropin receptor antibody.
The severity of Hashimoto's disease (HD) and intractability of Graves' disease (GD) varies among patients. Severity of HD is associated with the functional +874A/T polymorphism for interferon-gamma, an inflammatory cytokine. To clarify the association between functional polymorphisms in two other inflammatory cytokine genes [tumour necrosis factor (TNF)-alpha and interleukin (IL)-2] and the severity of autoimmune thyroid disease (AITD), we examined the TNF-alpha-1031T/C, TNF-alpha-857C/T and IL-2 -330T/G polymorphisms in genomic DNA samples. We genotyped 41 patients with intractable GD, 34 patients with GD in remission, 41 patients with severe HD, 36 patients with mild HD and 70 healthy controls. The frequency of carriers of TNF-alpha-1031C (CT + CC), which correlates with higher TNF-alpha production, was significantly higher in HD and GD patients than in controls, but was not associated with the severity of HD. In GD patients, the levels of anti-thyrotropin receptor antibody (TRAb) at onset of the disease was higher in patients with the TNF-alpha-857T (CT + TT) genotype, which correlates with higher TNF-alpha production, than in those with the -857CC genotype. We found no differences in the IL-2 -330T/G polymorphism among groups of AITD patients. In conclusion, the functional -1031T/C polymorphism of the TNFA gene is associated with the development of AITD and the functional -857C/T polymorphism is associated with the levels of TRAb in active GD patients.
Inoue
N
N
Department of Biomedical Informatics, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Watanabe
M
M
Nanba
T
T
Wada
M
M
Akamizu
T
T
Iwatani
Y
Y
D000208:Acute Disease; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology; D050031:Hashimoto Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011989:Receptors, Thyrotropin / Q000276:immunology; D018709:Statistics, Nonparametric; D013954:Thyroglobulin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D001323:Autoantibodies; D007376:Interleukin-2; D011989:Receptors, Thyrotropin; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013954:Thyroglobulin; D007453:Iodide Peroxidase