Functional polymorphisms inTBX21andHLXare associated with development and prognosis of Graves' disease

Abstract

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.

Functional polymorphisms affecting Th1 differentiation are associated with the severity of autoimmune thyroid diseases

“…We previously reported that Th17 cells and inflammatory cytokines, such as IL-1β, that induce Th17 differentiation were associated with the intractability of GD [8,39,40]. We also reported that lower genetic expression of TBX21, which promotes the differentiation of Th1, was associated with the intractability of GD [11], probably because IFN-γ, a Th1 cytokine, potently inhibits the development of Th17 cells [41]. Therefore, we suggest that higher production of IL-18 may attenuate the intractability of GD through the enhancement of IFN-γ production.…”

“…We previously reported that CD8 + CD25 + activated cytotoxic T cells and Th1 cells were increased in patients with severe HD [8,9] and that higher production of IFN-γ was more frequent in patients with severe HD than in those with mild HD [10]. Moreover, lower expression of T-box 21 (TBX21), the master transcription factor of Th1 cells, was associated with intractability of GD [11]. These data suggest that genetic differences in immune mediating factors that regulate Th1 cells may be associated with the prognosis of AITD.…”

TBX21-1993T/C (rs4794067) polymorphism is associated with increased risk of chronic periodontitis and increased T-bet expression in periodontal lesions, but does not significantly impact the IFN-g transcriptional level or the pattern of periodontophatic bacterial infection

“…In this aspect our result are in accordance with published evidence. 25,26 However, it is important to notice that despite the strong influence of T allele/genotypes over T-bet expression ( 2 fold), the subsequent impact over IFN-g expression was significantly lower (1.21-fold), and proved statistically non-significant.…”

TBX21-1993T/C polymorphism association with Th1 and Th17 response at periapex and with periapical lesions development risk

“…Therefore, patients with theoretical resistance or susceptibility to apical periodontitis development present distinct frequencies of TBX21‐1993 genotypes/alleles, being the polymorphic C allele, and TC and TC+CC genotypes, associated with decreased risk to develop periapical lesions. Interestingly, previous case‐control studies demonstrate that TBX21‐1993T/C influence the risk at different conditions, such as hepatitis, lupus erythematosus, and asthma …”