Absence of linkage between 5q markers and serum IgE levels in four large atopic families

Background - Both genetic and environmental influences have been suggested to control the immunoglobulin (Ig)E response to allergens and, as a result, provide susceptibility to atopic disease. Two recent reports suggested that a major gene controlling basal IgE levels in humans was transmitted in a pattern consistent with autosomal recessive inheritance and was located on the long arm of chromosome 5 in the interleukin (IL)-4 gene complex. Objective - The purpose of this report is to evaluate evidence for linkage of IgE with polymorphic genetic markers in the candidate region of 5q in four large pedigrees originally selected for studies of atopy. Method - Four large, highly characterized pedigrees in which IgE levels had been determined and genotypes at markers in the 5q candidate region were evaluated using both lod score and sib pair methods of analysis. Results - In these pedigrees, we reject close to moderate linkage (up to 5 cM) of an IgE locus with markers on 5q. Conclusion - The genetic aspects of IgE regulation and its role in atopy remain controversial. The data suggest that should major genes be involved in the inheritance of atopy susceptibility, they are likely to be multiple in number and likely to involve interaction with other (exogenous) environmental exposures.