The Journal of Allergy and Clinical Immunology
Volume 115, Issue 1 , Pages 80-87, January 2005

Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes

  • Maritta Pykäläinen, MSc

      Affiliations

    • Turku Centre for Biotechnology, University of Turku and Åbo Akademi University
    • Turku Graduate School of Biomedical Sciences
    • Corresponding Author InformationReprint requests: Maritta Pykäläinen, MSc, Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, PO Box 124, FIN-20520, Turku, Finland.
    • ,
  • Riikka Kinos, PhD

      Affiliations

    • Turku Centre for Biotechnology, University of Turku and Åbo Akademi University
    • ,
  • Sanna Valkonen, MSc

      Affiliations

    • Turku Centre for Biotechnology, University of Turku and Åbo Akademi University
    • ,
  • Pia Rydman, PhD

      Affiliations

    • GeneOS Ltd, Helsinki
    • ,
  • Maritta Kilpeläinen, MD, PhD

      Affiliations

    • Department of Pulmonary Diseases and Clinical Allergology, Turku
    • ,
  • Lauri A. Laitinen, MD, PhD

      Affiliations

    • Department of Pulmonary Medicine, Helsinki University Central Hospital
    • ,
  • Jussi Karjalainen, MD, PhD

      Affiliations

    • Department of Respiratory Medicine
    • ,
  • Markku Nieminen, MD, PhD

      Affiliations

    • Department of Respiratory Medicine
    • ,
  • Mikko Hurme, MD, PhD

      Affiliations

    • Department of Microbiology and Immunology, Tampere University Hospital
    • ,
  • Juha Kere, MD, PhD

      Affiliations

    • Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki
    • Department of Biosciences at Novum, Karolinska Institute, Stockholm
    • ,
  • Tarja Laitinen, MD, PhD

      Affiliations

    • GeneOS Ltd, Helsinki
    • Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki
    • ,
  • Riitta Lahesmaa, MD, PhD

      Affiliations

    • Turku Centre for Biotechnology, University of Turku and Åbo Akademi University

Received 15 January 2004; received in revised form 27 September 2004; accepted 4 October 2004.

Turku, Helsinki, and Tampere, Finland, and Stockholm, Sweden

Background

Immune responses characterized by TH2 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 naïve CD4+ T cells into either TH1 or TH2 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 TH1/TH2 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 TH1/TH2 mediated diseases will be of great interest.

Key words: Association analysis, common variant, STAT6, GATA3, STAT4, asthma, serum IgE, haplotype

Abbreviations used: DHPLC, Denaturing high-performance liquid chromatography, GATA3, GATA-binding protein 3, HPM, Haplotype Pattern Mining, ILR, Interleukin receptor, SNP, Single nucleotide polymorphism, STAT4, Signal transductor and activator of transcription 4, STAT6, Signal transductor and activator of transcription 6, UTR, Untranslated region

 

 Supported by grants from the Academy of Finland, National Technology Agency (TEKES), Väinö and Laina Kivi's Foundation, The Finnish Society of Allergology and Immunology, Ida Montin Foundation, and Turku University Hospital Fund.

PII: S0091-6749(04)02625-9

doi:10.1016/j.jaci.2004.10.006

The Journal of Allergy and Clinical Immunology
Volume 115, Issue 1 , Pages 80-87, January 2005

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