CTLA-4 CT60 polymorphism in thyroid and polyglandular autoimmunity.
Autoimmune thyroid diseases (AITDs) frequently occur together with other endocrine autoimmune conditions, denominated as polyglandular autoimmunity (PGA). The cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene was recently associated with AITD and PGA, and the CTLA-4 protein is a strong inhibitor of T-cells.The tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine. This study aimed to analyze the association of the CTLA-4 CT60 and TNF-alpha-863 polymorphisms with PGA. Homogeneous groups of 70 patients with AITD, 70 with type 1 diabetes (T1D), 70 with both AITD and T1D (PGA), and 100 healthy controls were genotyped for the CTLA-4 CT60 and TNF-alpha-863 polymorphisms by minisequencing on an ABI PRISM-3100 genetic analyzer. The CT60 G/G genotype was significantly more common in patients with PGA than in healthy controls (48.6 % vs. 32.0 % , OR = 2.01, 95 % CI = 1.07-3.77, p = 0.038). The CT60 allele frequencies differed as well between PGA patients and controls, with the predisposing G allele being increased in PGA (OR = 1.63, 95 % CI = 1.03-2.55, p = 0.042). Patients with PGA did not differ from those with AITD (p = 0.602) or T1D(p = 0.362). For TNF-alpha-863, carriers of the minor A allele occurred more frequently in the T1D group than in controls (47.1 % vs. 33 % , OR = 1.81, 95 % CI = 0.97-3.39, p = 0.079), but no differences in allele or genotype distribution were noted between PGA patients and controls (p = 0.886 and 0.389, respectively). In conclusion the CTLA-4 CT60 polymorphism is associated with PGA.
Dultz
G
G
Department of Medicine I, Gutenberg University, Mainz, Germany.
Matheis
N
N
Dittmar
M
M
Bender
K
K
Kahaly
G J
GJ
D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013959:Thyroid Diseases / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D044465:White People / Q000235:genetics
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D014409:Tumor Necrosis Factor-alpha