A polymorphism in gasdermin B (GSDMB) gene is associated with severe asthma exacerbations in childhood: A population-based birth cohort study

摘要

Rationale. Markers on chromosome 17q12 have been associated withchildhood asthma in genome-wide association studies. Objective.We investigated the association of a single nucleotide polymorphism(SNP) in GSDMB (rs7216389) on 17q12 with asthma presence andseverity in a population-based birth cohort study. Methods. Childrenwere followed from birth to age 8 years. Data on parentally-reportedsymptoms were collected using an interviewer-administered questionnaireat age 1, 3, 5 and 8 years. Atopy was assessed by skin testing at age3, 5 and 8 years. Information on asthma/wheeze hospital admissionsand severe asthma exacerbations was collected from child’s primarycare medical record. Data were analyzed as a recessive genetic model,with T-allele homozygotes as the risk group. Results. Compared to Callele carriers, T-allele homozygotes of rs7216389 were signifi cantlymore likely to: wheeze at age 3, 5 and 8 years; have persistent wheeze(OR 1.69, 95% CI 1.05-2.71, p=0.03); have frequent episodes of wheezingand be on asthma medication. In a multiple logistic regressionmodel adjusted for gender, atopic sensitisation and maternal smoking,T allele homozygotes were signifi cantly more likely to be hospitalized(aOR 2.20 [1.22-3.99], p=0.0009) with Cox regression hazard ratiofor T-allele homozygotes of 1.94 [1.13-3.33], p=0.016. Results of Coxregression analysis investigating the eff ect of genotype on the age offi rst severe exacerbation of asthma indicated an overall hazard ratioof severe asthma exacerbation among T-allele homozygotes of 1.53[1.04-2.27], p=0.03. Conclusions. Th is is the fi rst population-basedbirth cohort study to confi rm that the risk of childhood wheeze andsevere asthma/wheeze exacerbations is increased among rs7216389TT homozygotes.