T cell-specific T-box transcription factor haplotype is associated with allergic asthma in children.
BACKGROUND
T cell-specific T-box transcription factor (T-bet) is a member of the T-box family of transcription factors regulating lineage commitment of T(H) lymphocytes toward a predominant T(H)1 phenotype. Asthma and allergy are common complex diseases characterized by T(H)2-mediated inflammation.


OBJECTIVE
We aimed to assess possible relationships between the T-bet gene (TBX21) and asthma and allergy in children.


METHODS
Twelve single nucleotide polymorphisms (SNPs) in the TBX21 region were genotyped in 948 children from the Environment and Childhood Asthma study. Allele and haplotype frequencies were compared in children with and without asthma (by 10 years) and allergy (> or =1 positive skin prick test response), as well as for the quantitative traits bronchial hyperresponsiveness determined by means of methacholine bronchial challenge testing, lung function determined by means of forced flow volume loops, fractional exhaled nitric oxide measurement, eosinophil count, and serum total IgE level.


RESULTS
Allergic asthma was significantly associated with 2 of the tested SNPs (rs11650354 and rs16947078) and further associated with the particular haplotype including these SNPs, with homozygote status resulting in an odds ratio of 8.3 (95% CI, 2.5-26.9) for allergic asthma. Neither nonallergic asthma or "allergy alone" nor the remaining quantitative variables were associated with TBX21 SNPs or haplotypes.


CONCLUSIONS
An association between a specific TBX21 haplotype and allergic asthma in children is demonstrated for the first time and might explain previously detected associations between SNPs within TBX21 and asthma and bronchial hyperresponsiveness.
Munthe-Kaas
Monica Cheng
MC
Department of Paediatrics, Ullevål University Hospital, Oslo, Norway. m.c.munthe-kaas@medisin.uio.no
Carlsen
Kai Håkon
KH
Håland
Geir
G
Devulapalli
Chandra Sekhar
CS
Gervin
Kristina
K
Egeland
Thore
T
Carlsen
Karin Lødrup
KL
Undlien
Dag
D
D000280:Administration, Inhalation; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000453:epidemiology / Q000235:genetics / Q000276:immunology; D002648:Child; D004804:Eosinophils / Q000166:cytology; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012129:Respiratory Function Tests; D012882:Skin Tests; D020825:T-Box Domain Proteins / Q000235:genetics*; D000098815:T-bet Transcription Factor
D000485:Allergens; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007073:Immunoglobulin E