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Atopy, respiratory function and HLA-DR in Aboriginal Australians.
Miriam F Moffatt1, Jennie A Faux, Susan Lester
1Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK. miriam@well.ox.ac.uk
Human Molecular Genetics
|March 7, 2003
Summary
The HLA-DRB1 gene locus significantly influences allergic asthma markers like IgE in Aboriginal Australians with hookworm infection. These effects are much stronger than in Caucasians, suggesting adaptation to parasites drives genetic predisposition to allergies.
Area of Science:
- Human Genetics
- Immunology
- Epidemiology
Background:
- The Major Histocompatibility Complex (MHC) Class II genes are linked to atopic phenotypes in Western populations.
- Asthma, while considered a Western disease, shares traits like elevated Immunoglobulin E (IgE) with parasitic infections.
Purpose of the Study:
- To investigate the association between the HLA-DRB1 locus and asthma, including intermediate phenotypes, in Aboriginal Australians with endemic hookworm infection.
- To explore the role of helminth infection in the genetic predisposition to allergic diseases.
Main Methods:
- Examined HLA-DRB1 alleles in Aboriginal individuals from the Kimberly region, Australia.
- Assessed asthma and allergic markers including skin test positivity to house dust mite (HDM), specific IgE to HDM, and total serum IgE.
- Utilized multi-allelic tests of association to determine locus effects on IgE variance, excluding genetic admixture.
Main Results:
- HLA-DRB1 alleles did not predict asthma presence.
- The HLA-DRB1 locus explained approximately 33% of the variance in total serum IgE and 17% in specific IgE to HDM.
- Observed MHC effects on IgE levels were significantly greater (an order of magnitude) than those reported in Caucasian populations.
Conclusions:
- The findings support the hypothesis that genetic predisposition to allergic diseases may be influenced by adaptation to helminth infections.
- Parasitism itself does not appear to confer protection against asthma.
- Stronger MHC effects on IgE in this population suggest a significant role for parasitic exposure in shaping allergic responses.