INTERLEUKIN-9 - A CANDIDATE GENE FOR ASTHMA

Asthma is a complex heritable inflammatory disorder of the airways ass ociated with clinical signs of atopy and bronchial hyperresponsiveness . Recent studies localized a major gene for asthma to chromosome 5q31- q33 in humans. Thus, this segment of the genome represents a candidate region for genes that determine susceptibility to bronchial hyperresp onsiveness and atopy in animal models. Homologs of candidate genes on human chromosome 5q31-q33 are found in four regions in the mouse genom e, two on chromosome 18, and one each on chromosomes 11 and 13. We ass essed bronchial responsiveness as a quantitative trait in mice and fou nd it linked to chromosome 13. Interleukin 9 (IL-9) is located in the linked region and was analyzed as a gene candidate. The expression of IL-9 was markedly reduced in bronchial hyporesponsive mice, and the le vel of expression was determined by sequences within the qualitative t rait locus (QTL). These data suggest a role for IL-9 in the complex pa thogenesis of bronchial hyperresponsiveness as a risk factor for asthm a.