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Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood.

Abstract：

RATIONALE:An asthma predisposition locus on chromosome 17q12-q21 has recently been replicated in different ethnic groups. OBJECTIVES:To characterize the asthma and atopy phenotypes in early childhood that associate with the 17q12-21 locus. METHODS:The single nucleotide polymorphism (SNP), rs7216389, was genotyped in 376 of 411 children from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohort born to mothers with asthma together with 305 mothers and 224 fathers. Nineteen additional SNPs in the region were genotyped in the children. Investigator-diagnosed clinical endpoints were based on diary cards and clinic visits every 6 months and at acute symptoms from birth. Lung function, bronchial responsiveness, and sensitization were tested longitudinally from early infancy. MEASUREMENTS AND MAIN RESULTS:rs7216389 was significantly associated with the development of wheeze (hazard ratio 1.64 [1.05-2.59], P value = 0.03), asthma (hazard ratio, 1.88 [1.15-3.07], P = 0.01), and acute severe exacerbations (hazard ratio 2.66 [1.58-4.48], P value = 0.0002). The effect on wheeze and asthma was observed for early onset but not late onset of disease. The increased risk of exacerbations persisted from 1 to 6 years of age (incidence ratio 2.48 [1.42-4.32], P value = 0.001), and increased bronchial responsiveness was present in infancy and at 4 years of age, but not at 6 years. In contrast, rs7216389 conferred no risk of eczema, rhinitis, or allergic sensitization. CONCLUSIONS:Variation at the chromosome 17q12-q21 locus was associated with approximately twofold increased risk of recurrent wheeze, asthma, asthma exacerbations, and bronchial hyperresponsiveness from early infancy to school age but without conferring risk of eczema, rhinitis, or allergic sensitization. These longitudinal clinical data show this locus to be an important genetic determinant of nonatopic asthma in children.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Bisgaard H,Bønnelykke K,Sleiman PM,Brasholt M,Chawes B,Kreiner-Møller E,Stage M,Kim C,Tavendale R,Baty F,Pipper CB,Palmer CN,Hakonarsson H

doi

10.1164/rccm.200809-1436OC

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

179-85

issue

eissn

1073-449X

issn

1535-4970

pii

200809-1436OC

journal_volume

179

pub_type

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Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood.