Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | American Journal of Respiratory and Critical Care Medicine |
| Vol/bind | 179 |
| Udgave nummer | 3 |
| Sider (fra-til) | 179-85 |
| Antal sider | 7 |
| ISSN | 1073-449X |
| DOI | |
| Status | Udgivet - 2009 |
Bibliografisk note
Keywords: Airway Resistance; Asthma; Child; Child, Preschool; Chromosomes, Human, Pair 17; Denmark; Female; Follow-Up Studies; Forced Expiratory Flow Rates; Genetic Predisposition to Disease; Genetic Variation; Humans; Hypersensitivity, Immediate; Incidence; Infant; Infant, Newborn; Lung Volume Measurements; Male; Oximetry; Phenotype; Prognosis; Prospective Studies; Recurrence; Risk Factors; Time FactorsAdgang til dokumentet
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I: American Journal of Respiratory and Critical Care Medicine, Bind 179, Nr. 3, 2009, s. 179-85.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood
AU - Bisgaard, Hans
AU - Bønnelykke, Klaus
AU - Sleiman, Patrick M A
AU - Brasholt, Martin
AU - Chawes, Bo
AU - Kreiner-Møller, Eskil
AU - Stage, Malene
AU - Kim, Cecilia
AU - Tavendale, Roger
AU - Baty, Florent
AU - Pipper, Christian Bressen
AU - Palmer, Colin N A
AU - Hakonarsson, Hakon
N1 - Keywords: Airway Resistance; Asthma; Child; Child, Preschool; Chromosomes, Human, Pair 17; Denmark; Female; Follow-Up Studies; Forced Expiratory Flow Rates; Genetic Predisposition to Disease; Genetic Variation; Humans; Hypersensitivity, Immediate; Incidence; Infant; Infant, Newborn; Lung Volume Measurements; Male; Oximetry; Phenotype; Prognosis; Prospective Studies; Recurrence; Risk Factors; Time Factors
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1164/rccm.200809-1436OC
DO - 10.1164/rccm.200809-1436OC
M3 - Journal article
C2 - 19029000
SN - 1073-449X
VL - 179
SP - 179
EP - 185
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 3
ER -