CTLA-4 CT60 Polymorphism in Thyroid and Polyglandular Autoimmunity

Abstract

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-α) is a proinflammatory cytokine. This study aimed to analyze the association of the CTLA-4 CT60 and TNF-α -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-α -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-α -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.

Key words

autoimmune thyroid disease - polyglandular autoimmunity - CTLA-4 - TNF-α

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