Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population

Background Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezu elan population (estimated at 20%) and genetic markers are needed to identi fy populations at risk and plan intervention strategies. Objective To study the influence of the MHC class I and class Il genes in t he susceptibility to atopic asthma. Methods MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene ha plotype frequencies were determined in 135 Venezuelan mestizos, 71 belong t o 20 atopic asthmatic families and 64 unrelated controls. The index cases w ere 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Derma tophagoides farinae (Der f). To ascertain the genes associated with suscept ibility to atopy and/or asthma, two control groups were studied, 41 non-ato pic subjects with skin-prick negative test, and undetectable levels of spec ific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). Results MHC-class I genes analysis showed that HLA-Cw7 was absent in the as thmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.017, PC = 0.19) and 20.8% in the atopic control s (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB1*11 in the asthmatic patients compared with non-ato pic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC= 0.02). The re were no significant differences among asthmatic and atopic controls in t he frequency of HLA-DRB1*11 (25.6 vs 17.4%). In contrast, the HLA-DRB1*1101 + haplotypes were significantly higher in asthmatics compared with atopic a nd non-atopic controls (19.6% vs 2.2% vs 2.3%, PC < 0.05). The HLA-DRB1*110 1, DQA1*0501, DQB1*0301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC < 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic contr ols; however, it was higher in atopic asthmatics vs atopic controls Der p ( median, 58.7 vs 2.7 kU/L, P < 0.001) and Der f (median, 46.9 vs 2.7 kU/L, P < 0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. Conclusions We have identified an association between the haplotype HLA-DRB 1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequen cies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, i t may have a protective role for developing atopic asthma in the population studied.