Association of CT60 cytotoxic T lymphocyte antigen-4 gene polymorphism with thyroid autoantibody production in patients with Hashimoto's and postpartum thyroiditis

Abstract

Strong genetic contribution has been demonstrated to influence the development of autoimmune thyroid disease (AITD) as well as thyroid autoantibody production. In order to assess the relation between CT60 cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism and thyroid autoantibody production, we investigated 180 consecutive newly diagnosed patients with two forms of AITD, 105 with Hashimoto's thyroiditis (HT) and 75 with postpartum thyroiditis (PPT). We evaluated thyroid function, measured antibodies against thyroid peroxidase (TPO) and thyroglobulin (Tg), and determined CT60 CTLA-4 gene polymorphism. In HT, TPO antibody median value was significantly lower in the AA compared to the AG and GG genotypes (65, 122 and 319 U/ml, P<0.005), while the Tg antibody median value was lower in the AA compared to the AG genotype (91 and 189 U/ml, P<0.02). In PPT, the frequency of thyroid autoantibody-positive patients was higher among G-allele-carrying genotypes (P<0.04). Similar to HT, the TPO antibody median value was lower in the AA compared to the AG and GG genotypes (12, 130 and 423 U/ml, P<0.006). Hypothyroid PPT patients were more often thyroid autoantibody-positive (P<0.005) and the TPO antibody median value was higher compared to hyperthyroid PPT patients (500 and 32 U/ml, P<0.0001). The frequency of the G-allele was significantly higher among hypothyroid patients (P<0.05). Our data suggest that in both HT and PPT, the CT60 CTLA-4 gene polymorphism contributes importantly to thyroid autoantibody production. In PPT, the genotype also seems to influence thyroid function, as patients with the polymorphous allele are more prone to develop hypothyroid form of PPT.

Fig. 1

The relation of CT60 cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphism with the concentration of thyroid peroxidase antibodies (TPOAb) (a) and thyroglobulin antibodies (TGAb) (b) in patients with newly diagnosed Hashimoto's thyroiditis. Data are median values and quartiles. *P < 0·002 compared with the AA genotype and P < 0·04 compared with the AG genotype, **P < 0·02 compared with the AA genotype (Kruskal–Wallis analysis of variance test).

Fig. 2

The relation of CT60 cytotoxic T lymphocyte antigen-4 (CTLA-4) polymorphism with the concentration of thyroid peroxidase antibodies (TPOAb) (a) and thyroglobulin antibodies (TGAb) (b) in patients with newly diagnosed postpartum thyroiditis. Data are median values and quartiles. *P < 0·005 compared with the AA genotype (Kruskal–Wallis analysis of variance test).