title: Atopy, respiratory function and HLA-DR in Aboriginal Australians.
abstract: 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 approximately 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.
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford OX3 7BN, UK. miriam@well.ox.ac.uk
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.forename: Jennie A
authors.initials: JA
authors.lastname: Faux
authors.forename: Susan
authors.initials: S
authors.lastname: Lester
authors.forename: Peter
authors.initials: P
authors.lastname: Paré
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Randy
authors.initials: R
authors.lastname: Spargo
authors.forename: Alan
authors.initials: A
authors.lastname: James
authors.forename: A William
authors.initials: AW
authors.lastname: Musk
authors.forename: William O C M
authors.initials: WO
authors.lastname: Cookson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001249:Asthma / Q000097:blood / Q000235:genetics / Q000276:immunology; D001315:Australia; D002648:Child; D002675:Child, Preschool; D003233:Conjunctivitis, Allergic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000378:metabolism*; D006725:Hookworm Infections / Q000097:blood / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012044:Regression Analysis; D012119:Respiration; D012737:Sex Factors; D044465:White People
chemical_list: D015798:HLA-DR1 Antigen; D007073:Immunoglobulin E