title: STAT6 as an asthma candidate gene: polymorphism-screening, association and haplotype analysis in a Caucasian sib-pair study.
abstract: The human signal transducer and activator of transcription 6 (STAT6) gene represents one of the most promising candidate genes for asthma and other inflammatory diseases on the chromosomal region 12q13-q24. Therefore we screened all 23 exons, including parts of the neighbouring introns, as well as the promoter region for common polymorphisms and tested them for linkage/association with asthma and related traits (total serum IgE level, eosinophil cell count and SLOPE of the dose-response curve after bronchial challenge) in a Caucasian sib-pair study (108 families with at least two affected children). We could identify 13 single nucleotide polymorphisms (SNPs), which are all non-coding. A recently described dinucleotide (GT) repeat in exon 1 was also examined. Besides the confirmation of the four alleles described elsewhere we could identify a new one, named allele A5. Neither the SNPs nor the GT repeat showed linkage/association to asthma. Two intronic SNPs and one SNP in the 3'untranslated region of the gene showed weak association to total IgE levels (P = 0.0200, 0.0260 and 0.0280, respectively), whereas a significant association was found between a SNP in intron 18 and an increase in total IgE levels (P = 0.0070). However, the most promising effect was seen between allele A4 of the GT repeat polymorphism and an increase in eosinophil cell count (P = 0.0010). From these findings we conclude that the human STAT6 gene is rather involved in the development of eosinophilia and changes in total IgE levels than contributing to the pathogenesis of asthma.
authors.affiliation: GSF-National Research Centre for Environment and Health, Institute of Epidemiology, Ingolstaedter Landstrasse 1, D-85764 Neuherberg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Duetsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Sabine
authors.initials: S
authors.lastname: Loesgen
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohde
authors.forename: Norman
authors.initials: N
authors.lastname: Klopp
authors.forename: Nicole
authors.initials: N
authors.lastname: Herbon
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Janine
authors.initials: J
authors.lastname: Altmueller
authors.forename: Matthias
authors.initials: M
authors.lastname: Wjst
mesh_terms: D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D018900:Dinucleotide Repeats / Q000235:genetics; D005091:Exons; D006239:Haplotypes; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012129:Respiratory Function Tests; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators