Human Molecular Genetics, 2003, Vol. 12, No. 6 625-630
© 2003 Oxford University Press
Atopy, respiratory function and HLA-DR in Aboriginal Australians
1Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK, 2Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, South Australia, Australia, 3McDonald Research Laboratory and iCAPTURE Center, University of British Columbia, Vancouver, Canada, 4Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3052, Australia, 5Health Department of Western Australia, 189 Royal St, East Perth, Western Australia, 6004, Australia, 6Departments of Pulmonary Physiology and Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Western Australia 6009, Australia and 7Department of Public Health and Medicine, University of Western Australia, Perth, Western Australia 6009, Australia
Received November 4, 2002; Accepted January 9, 2003
The Class II genes of the MHC represent a major locus with quantified effects on atopic (allergic) phenotypes in many studies of westernized Caucasians. Although asthma is considered a disease of western societies, typical components of the asthma phenotype, such as elevations of the IgE, are seen with parasitic infestation. We have therefore investigated the effects of the HLA-DRB1 locus on asthma and its intermediate phenotypes in Aboriginal people from the Kimberly region of Australia who were suffering from endemic hookworm infection. Recognizable correlates of allergic asthma were present in the subjects, including skin test positivity to house dust mite (HDM), specific IgE responses to HDM, and the total serum IgE. HLA-DRB1 alleles did not predict the presence of asthma, but multi-allelic tests of association showed the locus accounted for 
33% of the variance of the total serum IgE concentration and 17% of the variance of the specific IgE titres to HDM. Genetic admixture was excluded as a cause of the results. These effects of the MHC on IgE levels were an order of magnitude greater than that seen in Caucasians, consistent with the hypothesis that the genetic predisposition to allergic disease may be driven by adaptation to helminth infection. The results further suggest that parasitism per se is not protective against asthma.
* To whom correspondence should be addressed. Tel: +44 1865287607; Fax: +44 1865287578; Email: miriam{at}well.ox.ac.uk
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