HLX1 gene variants influence the development of childhood asthma.

Authors:
Kathrin Suttner, Isabell Ruoss, Philip Rosenstiel, Martin Depner, Leonardo A Pinto, Michaela Schedel, Jerzy Adamski, Thomas Illig, Stefan Schreiber, Erika von Mutius, Michael Kabesch
Year of publication:
2009
Volume:
123
Issue:
1
Issn:
0091-6749
Journal title abbreviated:
J ALLERGY CLIN IMMUN
Journal title long:
Journal of allergy and clinical immunology
Impact factor:
12.485
Abstract: 
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.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.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).We investigated whether genetic variations in the HLX1 gene exist and whether these could affect the development of childhood asthma.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.