title: Evidence of a strong, positive association between atopy and the HLA class II alleles DR4 and DR7.
abstract: BACKGROUND
  Atopy, with or without associated asthma, provides a useful model for evaluating the genetic factors that control human immune responsiveness. HLA class II gene products are involved in the control of immune responses.
  
  
  OBJECTIVE
  We investigated whether susceptibility or resistance to the disease was associated with HLA class II genes.
  
  
  METHODS
  Blood samples were obtained from two groups of unrelated European-born white adults: 56 atopic patients (52 of them with asthma) and 39 healthy controls with no personal or familial history of asthma or atopy. Genomic DNA was extracted from peripheral blood lymphocytes. The exons of DQA1, DQB1, DRB and DPB1 genes were selectively amplified by the polymerase chain reaction (PCR) method. Genotyping was carried out by digestion of the amplified DNA products with allele-specific endonucleases (PCR-RFLP), which can recognize allelic variations in the polymorphic exon.
  
  
  RESULTS
  We found no significant differences in the frequency of DPB1 alleles between patients and controls. HLA class II DR4 and DR7 alleles were present in 39.2% of the patients and in 2.5% of the healthy subjects (Pc*2 < or = 3.9 10(-3)). Conversely, DQA1*0103 and DQB1*0502 alleles were more frequent in the control subjects. These results confirm a previous study of an extended pedigree, which showed that DR4 and DR7 alleles were absent in all healthy members of the family and were frequently observed in atopic and/or in asthmatic subjects.
  
  
  CONCLUSIONS
  We observed that HLA-DR 4 and DR7 alleles are significantly implicated in their susceptibility to the disease and suggest that this susceptibility is more related to atopy than to specific responses to allergens. According to previous studies, we could also submit that in atopic patients with asthma, DR4 alleles at the least, could be more closely associated with atopy than with asthma per se. Conversely, we suggest that some allelic DQA1 and DQB1 sequences might confer protection against the disease.
authors.affiliation: Laboratoire de Physiologie Respiratoire, Université Paris V, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Aron
authors.forename: N
authors.initials: N
authors.lastname: Desmazes-Dufeu
authors.forename: R
authors.initials: R
authors.lastname: Matran
authors.forename: B S
authors.initials: BS
authors.lastname: Polla
authors.forename: D
authors.initials: D
authors.lastname: Dusser
authors.forename: A
authors.initials: A
authors.lastname: Lockhart
authors.forename: E
authors.initials: E
authors.lastname: Swierczewski
mesh_terms: D000328:Adult; D000483:Alleles; D001249:Asthma / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000235:genetics; D059868:HLA-DP beta-Chains; D006683:HLA-DQ Antigens / Q000235:genetics; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D015804:HLA-DR4 Antigen / Q000235:genetics*; D015809:HLA-DR7 Antigen / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology*; D008297:Male; D012016:Reference Values
chemical_list: D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D015804:HLA-DR4 Antigen; D015809:HLA-DR7 Antigen; D000949:Histocompatibility Antigens Class II