J Med Genet 41:658-663 doi:10.1136/jmg.2004.020263
  • Original article

Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults

  1. S Weidinger1,6,
  2. N Klopp2,
  3. S Wagenpfeil3,
  4. L Rümmler1,
  5. M Schedel4,
  6. M Kabesch4,
  7. T Schäfer5,
  8. U Darsow1,
  9. T Jakob1,6,
  10. H Behrendt6,
  11. H E Wichmann2,
  12. J Ring1,6,
  13. T Illig2
  1. 1Department of Dermatology and Allergy Biederstein, Technical University Munich, Germany
  2. 2Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany
  3. 3Institute for Medical Statistics and Epidemiology, Technical University Munich, Germany
  4. 4University Childrens’ Hospital, Ludwig Maximilians University Munich, Germany
  5. 5Institute of Social Medicine, Medical University Lübeck, Germany
  6. 6Division of Environmental Dermatology and Allergy GSF/TUM, GSF National Research Center for Environment and Health & ZAUM Center for Allergy and Environment, Technical University Munich, Germany
  1. Correspondence to:
 Dr S Weidinger
 Department of Dermatology and Allergy, Technical University Munich, Biedersteiner St. 29, 80802 Munich, Germany;
  • Received 5 March 2004
  • Accepted 13 April 2004
  • Revised 9 April 2004


Background: Several studies have shown linkage of chromosome 12q 13–24 with atopy related phenotypes. Among candidate genes in this region is STAT6 (signal transducer and activator of transcription), which is essential for Th2 cell differentiation, recruitment, and effector function.

Methods: We evaluated six polymorphisms of STAT6 for evidence of associations with serum IgE levels and atopic diseases in a population based cross sectional cohort of 1407 German adults. Genotyping was performed using the matrix assisted laser desorption ionisation–time of flight mass spectrometry method. Haplotypes were estimated using the SAS/Genetics module, and population-derived IgE percentiles (50% IgE>53 kU/l, 66% IgE>99 kU/l and 90% IgE>307 kU/l) were modelled as outcome variables in haplotype trend regression analysis.

Results: All polymorphisms were genotyped successfully. Haplotype reconstruction revealed 8/64 possible haplotypes, reaching estimated frequencies of 1% or more. One polymorphism in intron 2 (rs324011) showed a significant association with total serum IgE (p = 0.015). A STAT6 risk haplotype for elevated IgE showing odds ratios of 1.7 (p = 0.015) for IgE cut-off 100 kU/l, and 1.54 (p = 0.032), 1.6 (p = 0.025), and 2.54 (p = 0.007) for IgE percentiles 50%, 66%, and 90%, respectively was detected. The increased risk of this haplotype was confirmed by linear haplotype trend regression on log transformed IgE values (p = 0.007). Analysis further revealed a risk haplotype for specific sensitisation and a risk haplotype for asthma.

Conclusion: The data indicate that genetic variants within STAT6 contribute significantly to IgE regulation and manifestation of atopic diseases.


  • Conflicts of interest: none declared