Single nucleotide polymorphisms in the STAT3 gene influence AITD susceptibility, thyroid autoantibody levels, and IL6 and IL17 secretion

Agnieszka Kotkowska; Ewa Sewerynek; Daria Domańska; Dorota Pastuszak-Lewandoska; Ewa Brzeziańska

doi:10.1515/cmble-2015-0004

Article

Single nucleotide polymorphisms in the STAT3 gene influence AITD susceptibility, thyroid autoantibody levels, and IL6 and IL17 secretion

Agnieszka Kotkowska , Ewa Sewerynek , Daria Domańska , Dorota Pastuszak-Lewandoska and Ewa Brzeziańska

Published/Copyright: March 25, 2015

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From the journal Cellular and Molecular Biology Letters Volume 20 Issue 1

Abstract

STAT3 (signal transducer and activator of transcription 3) is an important cellular effector in the Jak/STAT signaling pathway, which plays a pivotal role in human immune system regulation, mediating the effect of different cytokines. In the present study, we assessed the correlation between STAT3 polymorphisms (rs3816769 C>T and rs744166 A>G) and risk of the autoimmune thyroid diseases (AITDs) Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) in the Polish population. Moreover, we evaluated the association of polymorphisms with the thyroid autoantibody levels (TPOAb, TgAb, TRAb) and the correlation between circulating proinflammatory IL6 and IL17 cytokines and thyroid autoantibody levels. The study included 71 AITD patients with HT (n = 39) or GD (n = 32) and a control group (n = 40). DNA SNP genotyping was performed using TaqMan probes. Serum levels of thyroid autoantibodies, IL6 and IL17 were measured according to enhanced chemiluminescence (ECL) assay. Allele A of STAT3 SNP rs744166 A>G was significantly more frequent in both HT and GD patients, while allele G was significantly more frequent in the control group. Similarly, allele C and CC genotype of STAT3 SNP rs3816769 C>T were significantly more frequent in the control group in comparison to HT and GD patients. Significantly higher TgAb median values were associated with CT rs3816769 genotype in HT patients. Serum levels of IL6 and IL17 positively correlated with TPOAb in the HT group. Serum level of IL6 positively correlated with TPOAb in the AITD group. Both studied polymorphisms seem to play a significant role in susceptibility to AITD (HT and GD). STAT3 SNPs may influence TAb level in AITD patients.

Keywords : Autoimmune thyroid disease; STAT3; Single nucleotide polymorphism; Thyroid autoantibodies; TPOAb; TgAb; TRAb; Cytokines; IL6; IL17

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Received: 2014-8-22

Accepted: 2015-1-16

Published Online: 2015-3-25

Published in Print: 2015-3-1

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https://doi.org/10.1515/cmble-2015-0004

Keywords for this article

Autoimmune thyroid disease; STAT3; Single nucleotide polymorphism; Thyroid autoantibodies; TPOAb; TgAb; TRAb; Cytokines; IL6; IL17