title: HLX1 gene variants influence the development of childhood asthma.
abstract: 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.
authors.affiliation: University Children's Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Suttner
authors.forename: Isabell
authors.initials: I
authors.lastname: Ruoss
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Martin
authors.initials: M
authors.lastname: Depner
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Pinto
authors.forename: Michaela
authors.initials: M
authors.lastname: Schedel
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.forename: Michael
authors.initials: M
authors.lastname: Kabesch
mesh_terms: D001249:Asthma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000276:immunology; D012307:Risk Factors; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C084058:HLX protein, human; D018398:Homeodomain Proteins; D014157:Transcription Factors