Association of childhood allergic asthma with markers flanking the IL33 gene in Italian families.

Two recent indipendent large-scale GWAS of asthma reported the association of several markers comprising some on chromosome 9. In this region, flanking IL33 gene, we have previously found linkage of marker D9S286 with elevated IgE and SPT in Italian asthmatic families.Here we report a family transmission study with allergic asthma in 137 trios from North-Eastern Italy ascertained through an allergic asthmatic child. Association analyses was conducted by the transmission disequilibrium test (TDT).The phenotypes clinical asthma, total serum IgE levels, bronchial hyper-responsiveness to methacoline (BHR+), skin prick test positivity to common aeroallergens (SPT+), to house dust mites (SPT-HDM), and to graminae (SPT-GMN) were investigated. The SNPs rs1342326 and rs928413 analysed, were in Hardy-Weinberg equilibrium and in LD with each other (D'=0.95; R2=0.59). The observed minor allele frequency was 23% (minor allele:G, major allele:T) and 31% (minor allele:G, major allele:A) for rs1342326 and rs928413.TDT analysis showed a preferential transmission of the rs928413-G allele to individual with SPT (T:65, NT:43, p=0.034) and in particular with SPT-GMN (T:54, NT:33, p=0.024). No other association was found. Haplotype analyses showed that rs1342326-rs928413/T-G was preferentially transmitted to children affected by asthma (p=0.018), BHR+ (p=0.006), IgE (p=0.022), or SPT (p=0.015) and in particular by SPT-GMN (p=0.006).These results extend the association of 9p24 with allergic asthma traits indicating the possible role of IL33 as an “alarmin” signal to immune system.