Search for quantitative trait loci of atopy-associated immune responses using allergen-specific IgG1 as an "endophenotype".

Inherited atopic diseases of humans arise from adverse adaptive humoral responses to noninfectious environmental allergens. We previously reported that allergen-specific IgG1 provides more reliable heritability estimates for responses to allergens than total IgE. Genome scans were done for 91 Caucasian nuclear families with history of atopy for total IgE and IgG1 produced against a common major allergen from house dust mite, Der p 1. Suggestive associations for Der p 1-IgG1 production were found at 7 quantitative trait loci (QTL) (logarithm of the odds, LOD ≥ 1.23; p ≤ 0.009) with QTL-specific heritabilities of 73%–80%. Scans using total IgE found suggestive associations for 12 QTLs (LOD ≥ 1.44; p ≤ 0.004), but QTL-specific heritabilities only in the range of 30%–35%. Allergen-specific IgG1 is a suitable “endophenotype” to be used in searches for genes associated with atopy-associated humoral immune responses to common aeroallergens.