GENETIC-CONTROL OF SERUM IGE LEVELS AND ASTHMA - LINKAGE AND LINKAGE DISEQUILIBRIUM STUDIES IN AN ISOLATED POPULATION

Immunoglobulin E (IgE) concentration in serum is elevated in atopic di seases such as asthma, A large genomic region on chromosome 5 has prev iously been implicated in the control of IgE levels and bronchial hype rreactivity and may, therefore, harbor genes predisposing to asthma. I n an effort to confirm this linkage and to delimit the critical region , we took advantage of an isolated founder subpopulation in Finland to study genetic linkage and haplotype associations. Sixteen polymorphic markers, including the Interleukin-4 and -9 genes (IL4, IL9), were ph ysically ordered and genotyped in 157 nuclear families. Genetic linkag e studies involving sib- and cousin-pair analyses found no evidence of genetic linkage between markers in 5q and either serum IgE levels or asthma, Haplotype association studies were also performed, Although in itial inspection suggested the possibility of linkage disequilibrium i n the region of IL9, we developed a rigorous permutation test for asse ssing association and determined that the association was no greater t han would be expected by chance. Sequence analysis of the IL9 gene in three patients sharing a possibly conserved haplotype revealed a T113M coding polymorphism, but this variant showed no association with eith er serum IgE levels or asthma. We conclude that allelic variation at c hromosome 5q31 is not likely to contribute to inheritance of serum IgE levels or the development of asthma in this Finnish subpopulation.