HLX1 gene variants influence the development of childhood asthma

作者：Suttner Kathrin; Ruoss Isabell; Rosenstiel Philip; Depner Martin; Pinto Leonardo A; Schedel Michaela; Adamski Jerzy; Illig Thomas; Schreiber Stefan; von Murtius Erika; Kabesch Michael^*

来源：Journal of Allergy and Clinical Immunology, 2009, 123(1): 82-88.

DOI：10.1016/j.jaci.2008.09.047

• HLX1
• asthma
• association study
• genetic analysis
• functional promoter analysis

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 I 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. (J Allergy Clin Immunol 2009;123:82-8.)

• 出版日期2009-1