Genetic variation of TBX21 gene increases risk of asthma and its severity in Indian children

Abstract

T-box transcription factor protein (TBX21) is encoded by the TBX21 gene in human. It is crucial for naive T lymphocyte development, interferon-γ production, airway hyperresponsiveness and regulation of corticosteroid response in asthmatics. Polymorphisms rs4794067 and rs16947078 of TBX21 were found to be associated with acetylsalicylic acid-induced and allergic asthma, respectively. We examined whether sequence variants of TBX21 gene are associated with asthma and its severity in Indian population. In a hospital-based case-control study, 240 asthmatic children and 240 healthy controls were investigated for the association of TBX21 rs4794067 (C>T) and rs16947078 (G>A) polymorphisms with asthma and its severity using PCR-restriction fragment length polymorphism method. Heterozygous (CT) (odds ratio (OR)=2.33; P=0.001) and variant (TT) (OR=6.25; P=0.001) genotypes of rs4794067 were demonstrated significant risk of asthma. However, in asthma severity variant (TT) genotype revealed significant increase risk (intermittent: OR=5.9, P=0.001; mild: OR=8.0, P=0.001; moderate: OR=3.2, P=0.041; and severe: OR=43.6, P=0.001) in all subgroups. Furthermore, haplotypes TG (OR=2.83; P=0.001) and TA (OR=2.54; P=0.001) of TBX21 were associated with an increased risk of asthma. Conversely, rs16947078 G>A polymorphism was not associated with any asthma/asthma severity risk. These data suggest that TBX21 gene variation may modify individual's susceptibility to asthma and its severity in Indian population. However, further validation in large population-based studies is needed to confirm the finding.

Integrated Analysis of the ETS Family in Melanoma Reveals a Regulatory Role of ETV7 in the Immune Microenvironment

“…Among them, CD2 is a transmembrane glycoprotein typically known for its participation in the costimulatory pathway of T cell activation ( 58 ). TBX21 is essential for naive T lymphocyte development and interferon-gamma production ( 59 ). IL15 is identified as a cytokine that stimulates the proliferation of T lymphocytes ( 60 ).…”

“…The model had a relatively good predictive value in training and testing cohorts ( Figures 11D, F ). All six gene signatures were immune-related and regulated the proliferation, differentiation, migration, or activation of T cells ( 59 , 60 , 62 , 63 , 65 ). In addition, melanoma patients with low expression of these six gene signatures had a significantly shorter OS ( Supplementary Figure 5 ).…”

IFNG, FCER1A, PCDHB10 expression as a new potential marker of efficacy in grass pollen allergen-specific immunotherapy

“…It also enhances IFNG expression creating a synergistic loop [ 40 , 41 ]. A polymorphism of TBX21 resulting in its lower expression stimulates Th2 cytokine production and aggravates asthma symptoms [ 42 ]. GATA3 is a transcription factor with an important role in Th2 cell maturation and an opposite function to TBX21.…”

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 …”

“…Interestingly, previous case-control studies demonstrate that TBX21-1993T/C influence the risk at different conditions, such as hepatitis, lupus erythematosus, and asthma. 25,26 However, in the view of the complexity inherent to genetic association case-control studies, after the identification of positive genetic association of TBX21-1993 with the risk of developing apical periodontitis, we next evaluated whether the impact of such genetic variants on the lesions outcome could be derived from a Th1-polarizing effect in the lesions environment. Our results demonstrate that the TBX21-1993 C allele was associated with decreased Tbet and IFNg mRNA expression in the periapical lesions, in accordance with the classic description of Tbet essential role in IFNg transcription, 10 as well with the reports of decreased transcriptional activity of the Tbx21 promoter associated with TBX21-1993C allele.…”