Functional polymorphisms in TBX21 and HLX are associated with development and prognosis of Graves' disease

Abstract

Background. It has been indicated that T-box 21 (TBX21) and H 2.0-like homeobox (HLX) are transcription factors related to the differentiation of T helper 1 cells, whereas GATA-binding protein 3 is the master transcription factor of T helper 2 cells. Methods. We genotyped − 1514T/C (rs17250932) and − 1993T/C (rs4794067) polymorphisms of TBX21, − 742C/G polymorphism (rs2184658) of HLX and − 1420G/A polymorphism (rs1269486) of GATA3 in genomic DNA samples from Japanese patients; 51 patients with severe Hashimoto's disease (HD), 39 with mild HD, 66 with intractable Graves' disease (GD), in whom remission was difficult to induce, 47 with GD in remission and 79 healthy volunteers. Results. The T alleles of the TBX21 − 1514T/C and − 1993T/C polymorphisms were more frequent in patients with intractable GD than in those with GD in remission. Among individuals with the TBX21 − 1993TT genotype, the G allele of HLX − 742C/G polymorphism, which correlates with low HLX expression, was more frequent in patients with intractable GD than in those with GD in remission. Conclusions. Functional polymorphisms in TBX21 are associated with the development of autoimmune thyroid diseases and prognosis of GD, and a functional polymorphism in HLX in combination with the TBX21 polymorphism is also associated with the prognosis of GD.

Keywords::

• TBX21
• HLX
• single nucleotide polymorphism
• disease severity
• disease intractability

Acknowledgements

We are grateful to all of the subjects who kindly agreed to participate in this study. This work is supported by Grant-in-Aid for Scientific Research (KAKENHI).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.