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PURPOSE OF THE STUDY. To determine the association between the 17q12–q21 locus and various clinical characteristics of asthma and atopic sensitization during childhood.
STUDY POPULATION. The Copenhagen Prospective Study on Asthma in Childhood (COPSAC) included a birth cohort of 411 children born to mothers with a history of asthma. Three hundred seventy-six of these children underwent genotyping for a particular, single-nucleotide polymorphism (SNP), rs7216389, in the 17q12–q21 locus.
METHODS. Three hundred seventy-six children underwent genotyping for 20 SNPs, including rs7216389. Infants were enrolled at age 1 month and were seen once every 6 months until age 6 years. Parents recorded daily symptoms. End points included investigator-diagnosed asthma or atopic disease and objective measurements of lung function and atopic sensitization, at various follow-up points.
RESULTS. Homozygosity for the T allele at SNP rs7216389 was associated with experiencing wheezing (hazard ratio [HR]: 1.64 [95% confidence interval [CI]: 1.05–2.59]), asthma (HR: 1.88 [95% CI: 1.15–3.07]), and acute severe exacerbations (HR: 2.66 [95% CI: 1.58–4.48]). Significantly increased bronchial hyperresponsiveness was seen at ages 1 month and 4 years but not 6 years. However, increased risk of asthma exacerbations persisted through age 6 years (incidence ratio: 2.48 [95% CI: 1.42–4.32]). There was no increased risk for eczema, rhinitis, or atopic sensitization.
CONCLUSIONS. The rs7216389 SNP at the 17q12–q21 locus was associated with increased risk of asthma, asthma exacerbations, and bronchial hyperresponsiveness. However, it was not associated with any increased risk of atopic sensitization, eczema, or rhinitis.
REVIEWER COMMENTS. This particular polymorphism was shown previously to be associated with increased risk for developing asthma. The data from this study describe the clinical phenotype associated with this SNP in a population of infants and young children at increased risk for asthma. It seems to confer a specific risk for asthma without increased atopy. This study was performed with a selected population at high risk for asthma, and future research will need to determine whether these findings are replicable in the general population.
- Copyright © 2009 by the American Academy of Pediatrics