Asthma and wheezing are characterised by airway inflammation and reversible airflow obstruction, and seem to have multiple phenotypes that may differ on the basis of age of onset.¹ Boys are more prone to develop wheezing and asthma in the early years, whereas girls are more susceptible later in life.^2–4 Whether this difference is due to genetic, hormonal, or environmental factors is unclear. We have previously reported an increased risk of wheezing and sensitisation in boys, in agreement with other studies, but could also demonstrate an interaction exceeding additivity between male sex and parental allergic disease, particularly in children with persistent wheezing.⁵ This finding raised the hypothesis of a sex specific genetic influence on childhood wheezing.

The interleukin-9 receptor gene (IL9R), located on the pseudoautosomal region of X and Y chromosomes (Xq28 and Yq12^6,7), has previously been associated with asthma in two separate family based data sets.^8,9 Haplotype analyses of polymorphic microsatellite markers in one of the studies⁹ revealed significant associations, predominantly in females, which suggest that the influence may be sex specific. However, to our knowledge no study on associations between IL9R single nucleotide polymorphisms (SNPs) and asthma and allergy has yet been reported.

The IL9 receptor belongs to the haematopoietin receptor superfamily¹⁰ and is expressed on T cells, mast cells, macrophages, eosinophils, and neutrophils.^11,12 The receptor consists of a specific IL9Rα unit and the common γ_c subunit, which forms a heteromer upon IL9 binding and activates Janus kinases and STAT factors.^10,13 Signals from the IL9 receptor have been shown to be crucial for immunologic processes such as T cell development¹⁴ and prevention of apoptosis.^13,15 More specifically, IL9 may stimulate release of chemotactic factors from bronchial epithelial cells and smooth muscle cells. …