DETECTION OF A RECESSIVE MAJOR GENE FOR HIGH IGE LEVELS ACTING INDEPENDENTLY OF SPECIFIC RESPONSE TO ALLERGENS

The genetic control of the total IgE, the immunoglobulins E involved i n allergy, remains still unclear. Although high IgE levels were found to be determined by a recessive major gene in several studies, other m odes of inheritance were also reported. Moreover, at least two differe nt genetic mechanisms controlling the IgE regulation have been suggest ed: one involved in the specific IgE response and the other one in the nonspecific response. To better understand the genetic mechanisms con trolling IgE variation, we performed segregation analysis of IgE level s by ig -noring or taking into account the specific response to allerg ens (SRA). Analyses were conducted using the class D regressive model, in a sample of 234 Australian nuclear families randomly selected duri ng the winter months, when IgE levels are the lowest (basal). SRA, whe n included as a covariate in the model, was defined by one of the thre e following criteria: (1) raised specific IgE level for one or more al lergens, (2) positive skin test for one or more allergens, and (3) at least one of the (1) or (2) criteria. When the presence of SRA is igno red, the familial transmission of total IgE level is compatible with t he segregation of a recessive major gene and residual familial correla tions. When the presence of SRA is accounted for in the analysis, whet her defined by criteria (1), (2), or (3), there is still evidence for a recessive major gene controlling IgE levels but residual familial co rrelations are no longer significant. In addition, no interaction betw een this major gene and SRA is shown hen. Our results suggest that thi s gene, which accounts for 28% of the variation of the trait, may be i nvolved in the control of basal IgE production, independently of speci fic response to allergens. (C) 1995 Wiley-Liss, Inc.