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Open Access Green as soon as Postprint is submitted to ZB.
HLX1 gene variants influence the development of childhood asthma.
J. Allergy Clin. Immunol. 123, 82-88:e6 (2009)
BACKGROUND: Major transcription factors controlling T(H)1 and T(H)2 development, such as T-box transcription factor and GATA3, might be centrally involved in asthma and atopic diseases. Only recently, the homeobox transcription factor H.20-like homeobox 1 (HLX1), interacting closely with T-box transcription factor, has been identified as an important regulator of T(H)1 differentiation and suppressor of T(H)2 commitment. OBJECTIVE: We investigated whether genetic variations in the HLX1 gene exist and whether these could affect the development of childhood asthma. METHODS: The HLX1 gene was resequenced in 80 chromosomes. Associations between identified polymorphisms, asthma, and atopic diseases were investigated in German children (total n = 3099) from the cross-sectional International Study of Asthma and Allergy in Childhood phase II. Functional properties of polymorphisms were studied by using luciferase reporter gene assays and electrophoretic mobility shift assays in T cells. All statistical analyses were performed with SAS/Genetics software (SAS Institute, Inc, Cary, NC). RESULTS: Nineteen polymorphisms were identified in the HLX1 gene, and 2 tagging single nucleotide polymorphisms representing 7 polymorphisms were associated with childhood asthma in our study population. Two promoter polymorphisms, C-1407T and C-742G, contained in 1 tagging block were associated with asthma (odds ratio, 1.44; 95% CI, 1.11-1.86; P = .0061), significantly decrease promoter transactivation, and disrupt specificity protein-transcription factor binding in in vitro experiments. CONCLUSIONS: Our data suggest that polymorphisms in the HLX1 gene increase the risk for childhood asthma. On the cellular level, altered binding of specificity protein-transcription factors to the HLX1 promoter and subsequent changes in HLX1 gene expression might contribute to these effects.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
HLX1; asthma; association study; genetic analysis; functional promoter analysis
Language
english
Publication Year
2009
HGF-reported in Year
2008
ISSN (print) / ISBN
0091-6749
e-ISSN
1097-6825
Quellenangaben
Volume: 123,
Issue: 1,
Pages: 82-88,
Article Number: e6
Publisher
Elsevier
Publishing Place
Amsterdam [u.a.]
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)
Institute of Epidemiology (EPI)
Institute of Epidemiology (EPI)
POF-Topic(s)
30201 - Metabolic Health
30503 - Chronic Diseases of the Lung and Allergies
30503 - Chronic Diseases of the Lung and Allergies
Research field(s)
Genetics and Epidemiology
PSP Element(s)
G-500600-004
G-503900-003
G-503900-003
Scopus ID
58149138845
Erfassungsdatum
2008-12-31