An assessment of the association between childhood asthma and HLA DRB1*03 using extended haplotype analysis.
Ancestral haplotypes between human leukocyte antigen (HLA) class I and class II alleles are well-recognized in the literature. We previously published a positive association between the class II HLA allele DRB1*03 and the subsequent development of asthma in a retrospective cohort of 383 children. To refine this association, we investigated whether DRB1*03-specific haplotypes extending across the HLA are associated with asthma incidence. We found evidence of strong HLA DRB1*03-dependent linkage disequilibrium across the region, but no association between DRB1*03 ancestral haplotypes and childhood asthma. We did, however, observe a trend toward a positive association between HLA DRB1*03 and asthma by adding non-ancestral DRB1*03 positive haplotypes. Our results suggest that the role of the HLA DRB1*03 in asthma susceptibility is independent of ancestral-haplotype-mediated linkage disequilibrium.
Hanchard
N A
NA
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Jacobson
R M
RM
Poland
G A
GA
Juhn
Y J
YJ
D001249:Asthma / Q000235:genetics* / Q000276:immunology; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006239:Haplotypes / Q000235:genetics* / Q000276:immunology; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D012189:Retrospective Studies
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains