No linkage and association of atopy to chromosome 16 including the interleukin-4 receptor gene

Background: Several susceptibility genes for atopy have been suggested in r ecent years. Few have been investigated as intensively as the interleukin-4 -receptor oc (IL4R alpha) gene on chromosome 16. The results remain in disp ute. Therefore, in a robust design, we tested for association of type I all ergy to the IL4R variations 150V and Q576R, and investigated chromosome 16 for atopy candidate regions in general. Methods: We identified 100 Danish allergy sib-pair families. Five conservat ive phenotypes for type I allergy were defined and evaluated. The IL4R vari ations were genotyped in trios and evaluated by the transmission disequilib rium test (TDT). Multipoint linkage analysis and exclusion mapping were con ducted with sib-pairs analyzed for 17 microsatellite markers. Results: No evidence for association or linkage to the IL4R polymorphisms w as found (P values: 0.12-0.90). Linkage analysis did not support linkage of any of the phenotypes to chromosome 16. Major parts of chromosome 16 were excluded as candidate regions harboring oligogenes for type I allergy. Conclusions: We found chromosome 16 unlikely to harbor strong candidate gen es for type I allergy. The role of the IL4Ra gene in the inheritance of ato py was insignificant in the Danish population. The use of conservative alle rgy phenotypes in the search for genes predisposing to atopic disease was d iscussed.