Indication of linkage of serum IgE levels to the interleukin-4 gene and exclusion of the contribution of the (-590 C to T) interleukin-4 promoter polymorphism to IgE variation

Previous segregation analysis of a sample of 234 randomly selected Australi an families showed evidence for a recessive major gene controlling serum im munoglobulin E (IgE) levels independently of the specific response to aller gens (SRA). Since linkage has been recently reported between serum IgE leve ls and the 5q candidate region spanning the interleukin-4 (IL-4) gene, we i nvestigated whether the recessive major gene detected by segregation analys is was linked to the IL-4 region and whether polymorphisms within the IL-it gene were associated with IgE levels. Both sib-pair method and combined se gregation and linkage analysis using the regressive models were applied to our data. Whereas there was no evidence of linkage of total IgE levels to t he IL-l region, an indication of linkage (P values ranging between 0.01 and 0.03) was found between IgE levels adjusted for SRA and two IL-4 polymorph isms: one dinucleotide repeat in intron 2 of the IL-4 gene and a single nuc leotide (-590 C to T) polymorphism in the IL-4 promoter. However, the putat ive IL-4 linked gene did not appear to be in linkage disequilibrium with ei ther of these two polymorphisms. A contribution of the IL-4 promoter polymo rphism, presumed to be a potential functional variant influencing IgE varia tion, was also excluded. (C) 1999 Wiley-Liss, Inc.