Human Molecular Genetics Advance Access published online on May 21, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm131
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Genetic haplotypes of Th-2 immune signalling link allergy to enhanced protection to parasitic worms
1 Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, SA2 8PP, UK 2 Institute of Parasitology, Shanghai, China
* Corresponding author: Julian M. Hopkin, School of Medicine, University of Wales, Swansea, Swansea SA2 8PP, UK. Ph: +44-1792-513062, Fax: +44-1792-513054, Email: J.M.Hopkin{at}swansea.ac.uk
Received March 2, 2007; Revised May 10, 2007; Accepted May 10, 2007
Parasitic worm infection, allergy and asthma involve increased IgE production, eosinophil activity, mucus secretion, and smooth muscle reactivity, effected through Th-2 immune signalling. These pathological features of allergic disorder, common in developed countries, appear to be protective features in resistance to parasitic worm infections prevalent in many developing countries. We investigated how genetic variation in the Th-2 signalling transduction molecule STAT-6 relates to these clinical disorders, using immune phenotyping by serum IgE levels, and haplotyping 9 STAT-6 genetic variants in a rural Chinese population, where Ascaris infection is prevalent, and an urban UK population where Ascaris is largely unknown but asthma and allergy are prevalent. We show for the first time that STAT6 haplotypes relate clearly to IgE levels, allergy and worm burden. The haplotypes segregated into two groups: those with raised IgE/low worm burden tended to have increased risk of allergic disorder, whilst low IgE/high worm burden tended to have a reduced risk of allergies. By estimating the mean worm burden for each haplotype in China and the relative risk of asthma for the matching haplotype in the UK we draw a cross-population comparison and show a negative correlation between worm burden and expected risk of asthma. These data imply that the origin of common up-regulating of Th-2 signalling, involving STAT-6, promotes asthma and allergy in developed countries, whereas in developing countries it protects against parasitic worm infections. Selective evolutionary mechanisms, driven by parasitic worm infection, may underlie the genetic contribution to risk of allergy and asthma in humans.
3 Present address: Division of Allergy and Clinical Immunology, The Johns Hopkins University, Baltimore, MD 21224, USA
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