title: Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes.
abstract: BACKGROUND
  Immune responses characterized by T H 2 type cells and IgE are important for the development of asthma and atopy. The transcription factors STAT6, GATA3, and STAT4 mediate the cytokine-induced development of naive CD4 + T cells into either T H 1 or T H 2 type.
  
  
  OBJECTIVE
  We studied genetic variation of the STAT6, GATA3, and STAT4 genes and examined whether single nucleotide polymorphisms (SNPs) in these loci were associated with asthma or serum high IgE levels in the Finnish asthmatic families.
  
  
  METHODS
  With denaturing high-performance liquid chromatography we screened all exons and exon-intron boundaries of the genes in 14 to 22 patients. All identified SNPs were genotyped in 120 nuclear families, and the haplotypes were analyzed by Haplotype Pattern Mining based statistical analysis. When potential association was observed, the analysis was replicated among 245 asthmatic patients and 405 population-based control subjects.
  
  
  RESULTS
  A total of 23 SNPs were identified, of which 8 were not previously listed in the SNP database. Interestingly, a haplotype analysis of GATA3 showed 3 related haplotypes that associated with different asthma and atopy related phenotypes among both the family and case-control data sets. For STAT6 and STAT4, no significant association to asthma or serum total IgE levels was observed.
  
  
  CONCLUSIONS
  We identified a panel of novel SNPs in genes coding for proteins important in the T H 1/T H 2 cell differentiation. SNPs of the GATA3 gene showed an initial association to asthma-related phenotypes. Elucidation of the importance of the identified panel of SNPs in other T H 1/T H 2 mediated diseases will be of great interest.
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Abo Academic University, Finland. maritta.pykalainen@btk.fi
authors.forename: Maritta
authors.initials: M
authors.lastname: Pykäläinen
authors.forename: Riikka
authors.initials: R
authors.lastname: Kinos
authors.forename: Sanna
authors.initials: S
authors.lastname: Valkonen
authors.forename: Pia
authors.initials: P
authors.lastname: Rydman
authors.forename: Maritta
authors.initials: M
authors.lastname: Kilpeläinen
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Laitinen
authors.forename: Jussi
authors.initials: J
authors.lastname: Karjalainen
authors.forename: Markku
authors.initials: M
authors.lastname: Nieminen
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Tarja
authors.initials: T
authors.lastname: Laitinen
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005387:Finland / Q000453:epidemiology; D050990:GATA3 Transcription Factor; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D050797:STAT4 Transcription Factor; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D007073:Immunoglobulin E