Editors' choiceT cell–specific T-box transcription factor haplotype is associated with allergic asthma in children
Section snippets
Study design and subjects
The present study is based on a 10-year follow-up of children in the 1992-1993 prospective birth cohort Environment and Childhood Asthma study in Oslo, Norway, described elsewhere.14 This follow-up study (2001-2004) was attended by 1019 (84%) of the 1215 children who had been examined with lung function measurements taken at birth (n = 802), included in a nested case-control study for bronchial obstruction at 2 years (n = 526), or both. The investigations in the 10-year follow-up included
Results
The mean age of all subjects included in the study was 10.8 (SD, 0.8) years, 54% were boys, 30% had asthma, 29% were allergically sensitized, 11% had allergic asthma, and 19% had nonallergic asthma. In addition, 32% exhibited BHR, and 21% had total IgE levels of greater than 179 kU/L. Demographic data for the allergic asthma group, nonallergic asthma group, control group, and total study group are presented in Table I. All tested SNPs were in Hardy-Weinberg equilibrium.
Discussion
The present study in 10-year-old children demonstrates an association between allergic asthma and 2 TBX21 SNPs, as well as the TBX21 haplotype 5′-GCCTGATCGCGT-3′ (including the 2 SNPs), where children homozygotic for the haplotype have an odds ratio of 8.3 for allergic asthma. There is no association between TBX21 polymorphisms and nonallergic asthma, “allergy alone,” or the quantitative variables IgE level, BHR, lung function, exhaled NO level, or serum eosinophil count.
The present finding of
References (34)
Gene-environment interactions in asthma and allergies: a new paradigm to understand disease causation
Immunol Allergy Clin North Am
(2005)- et al.
Asthma: T-bet—a master controller?
Curr Biol
(2002) - et al.
A new statistical method for haplotype reconstruction from population data
Am J Hum Genet
(2001) - et al.
T-bet inhibits both TH2 cell-mediated eosinophil recruitment and TH17 cell-mediated neutrophil recruitment into the airways
J Allergy Clin Immunol
(2007) - et al.
CFTR gene mutations and asthma in the Norwegian Environment and Childhood Asthma study
Respir Med
(2006) - et al.
T-bet/GATA-3 ratio is a surrogate measure of Th1/Th2 cytokine profiles and may be novel targets for CpG ODN treatment in asthma patients
Chin Med J (Engl)
(2006) - et al.
Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet
Science
(2002) - et al.
Decreased T-bet expression and changes in chemokine levels in adults with asthma
Clin Exp Immunol
(2007) - et al.
Costimulation through CD86 is involved in airway antigen-presenting cell and T cell responses to allergen in atopic asthmatics
J Immunol
(1998) - et al.
Genome screen for asthma and related phenotypes in the French EGEA study
Am J Respir Crit Care Med
(2000)
A genetic basis for IFN-gamma production and T-bet expression in humans
J Immunol
Association analysis of novel TBX21 variants with asthma phenotypes
Hum Mutat
Association study of 15 novel single-nucleotide polymorphisms of the T-bet locus among Finnish asthma families
Clin Exp Allergy
TBX21: a functional variant predicts improvement in asthma with the use of inhaled corticosteroids
Proc Natl Acad Sci U S A
Functional promoter polymorphism in the TBX21 gene associated with aspirin-induced asthma
Hum Genet
T-Bet polymorphisms are associated with asthma and airway hyperresponsiveness
Am J Respir Crit Care Med
The environment and childhood asthma (ECA) study in Oslo: ECA-1 and ECA-2
Pediatr Allergy Immunol
Cited by (0)
This study was performed within the ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood), which is part of GA2LEN (Global Allergy and Asthma European Network).
Supported by the Norwegian Research Council; the University of Oslo; the Eastern Norway Regional Health Authority; the Norwegian Foundation for Health and Rehabilitation; the Norwegian Association for Asthma and Allergy; the Kloster Foundation; Voksentoppen, Department of Paediatrics; Ullevål University Hospital; Pharmacia; AstraZeneca; and the Hakon group. The genetic analysis was financially supported by the University of Oslo, Norway; the National Programme for Research in Functional Genomics in Norway (FUGE); and the Eastern Norway Regional Health Authority.
Disclosure of potential conflict of interest: K. H. Carlsen has consulting arrangements with GlaxoSmithKline and is on the speakers' bureau for Novartis, Merck, and GlaxoSmithKline. C. S. Devulapalli has received grant support from AstraZeneca. K. L. Carlsen has consulting arrangements with Novartis, has received grant support from AstraZeneca and Pharmacia, and is on the speakers' bureau for GlaxoSmithKline, AstraZeneca, Merck, and the UCB Institute. The rest of the authors have declared that they have no conflict of interest.
- ∗
These authors contributed equally to this work.