EVIDENCE OF A STRONG, POSITIVE ASSOCIATION BETWEEN ATOPY AND THE HLA CLASS-II ALLELES DR4 AND DR7

Background Atopy, with or without associated asthma, provides a useful model for evaluating the genetic factors that control human immune re sponsiveness. HLA class II gene products are involved in the control o f immune responses. Objectives We investigated whether susceptibility or resistance to the disease was associated with HLA class II genes. M ethods Blood samples were obtained from two groups of unrelated Europe an-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. Th e exons of DQA1, DQB1, DRB and DPB1 genes were selectively amplified b y the polymerase chain reaction (PCR) method. Geno-typing was carried out by digestion of the amplified DNA products with allele-specific en donucleases (PCR-RFLP), which can recognize allelic variations in the polymorphic exon. Results We found no significant differences in the f requency of DPB1 alleles between patients and controls. HLA class II D R4 and DR7 alleles were present in 39.2% of the patients and in 2.5% o f the healthy subjects (Pc2 less than or equal to 3.9 10(-3)). Conver sely, DQA10103 and DQB1*0502 alleles were more frequent in the contro l subjects. These results confirm a previous study of an extended pedi gree, which showed that DR4 and DR7 alleles were absent in all healthy members of the family and were frequently observed in atopic and/or i n asthmatic subjects. Conclusion We observed that HLA-DR 4 and DR7 all eles are significantly implicated in their susceptibility to the disea se 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 asthm a per se. Conversely, we suggest that some allelic DQA1 and DQB1 seque nces might confer protection against the disease.