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

Author(s): Aida Semic-Jusufagic | Angela Simpson | Jenny Hankinson | Adnan Custovic

Journal: Acta Medica Academica
ISSN 1840-1848

Volume: 40;
Issue: 2;
Start page: 110;
Date: 2011;
Original page

Keywords: Childhood asthma | Genetics | rs7216389 | GSDMB | ORMDL3

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 questionnaire at age 1, 3, 5 and 8 years. Atopy was assessed by skin testing at age 3, 5 and 8 years. Information on asthma/wheeze hospital admissions and severe asthma exacerbations was collected from child’s primary care medical record. Data were analyzed as a recessive genetic model, with T-allele homozygotes as the risk group. Results. Compared to C allele carriers, T-allele homozygotes of rs7216389 were significantly more 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 wheezing and be on asthma medication. In a multiple logistic regression model adjusted for gender, atopic sensitisation and maternal smoking, T allele homozygotes were significantly more likely to be hospitalized (aOR 2.20 [1.22-3.99], p=0.0009) with Cox regression hazard ratio for T-allele homozygotes of 1.94 [1.13-3.33], p=0.016. Results of Cox regression analysis investigating the eff ect of genotype on the age of first severe exacerbation of asthma indicated an overall hazard ratio of 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-based birth cohort study to confirm that the risk of childhood wheeze and severe asthma/wheeze exacerbations is increased among rs7216389 TT homozygotes.

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