TBX21 gene variants (responsible for T-bet) may increase childhood asthma risk

T-box 21, also known as TBX21, is a human gene for T-bet transcription factor. T-bet is a bridge between innate and adaptive immunity (http://buff.ly/1aD6h8s).

The T cell-specific T-box transcription factor (TBX21) plays a crucial role in the regulation of the immune system because it induces the differentiation of T(H)1 and blocks T(H)2 commitment. TBX21 works together with the homeobox transcription factor HLX1.

The TBX21 gene was resequenced in 37 adult volunteers. The impact of combinations of TBX21 and HLX1 polymorphisms on the development of asthma was assessed by using a risk score model.


Single-nucleotide polymorphism: DNA molecule 1 differs from DNA molecule 2 at a single base-pair location (a C/T polymorphism). Image source: Wikipedia, David Hall, Creative Commons Attribution 2.5 License.

Forty-three polymorphisms were identified in the TBX21 gene. Three single nucleotide polymorphisms increased childhood asthma risk significantly.

In a risk score model, the combination of TBX21 and HLX1 polymorphisms increased the asthma risk by more than 3-fold.

SNPs associated with atopic diseases

Filaggrin gene

Filaggrin is essential for epidermal barrier function. SNP associated with eczema and asthma.

17q12-21 gene

ORMDL3 protein defects associated with asthma.

5q22-32 gene

CD14 is a lipopolysaccharide (LPS) receptor. SNPs associated with asthma and atopy.

3p21-22 gene

CCR5 is a chemokine receptor. SNP can be protective against asthma.

Xp22 gene

TLR7 and TLR8 are recognition receptors for viral ssRNA. SNPs assciated with asthma, rhinitis, atopic dermatitis.

5q31 gene

IL-13 is a cytokine that induces IgE secretion, mucus production, and collagen synthesis (fibrosis). SNPs associated with asthma.

ADRB2 gene

ADRB2 gene encodes β2-adrenergic receptor. Argenteum (Arg) or Arg/Arg phenotype associated with decreased albuterol response compared to Gly/Gly phenotype at residue 16.

ADAM33 gene

Type 1 transmembrane protein involved in cell-to-cell interactions. SNPs associated with asthma.

GLCCI1 gene, rs37972 variant
A variant in the glucocorticoid-induced transcript 1 gene (GLCCI1), rs37972, associated with a decrease in forced expiratory volume in 1 second (FEV1) in response to treatment with inhaled glucocorticoids (NEJM, 09/2011).

References:
TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants. Suttner K, Rosenstiel P, Depner M, Schedel M, Pinto LA, Ruether A, Adamski J, Klopp N, Illig T, Vogelberg C, Schreiber S, von Mutius E, Kabesch M. J Allergy Clin Immunol. 2009 Apr 9. [Epub ahead of print]
Genetics Suggest Asthma Is Not One Disease But "Umbrella" Term for Multiple Conditions
2 new asthma susceptibility genes: ORMDL3 and CHI3L1