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Genetic variation in uncontrolled childhood asthma despite ICS treatment

by Vijverberg, S J H , Leusink, M , Onland-Moret, N C , Raaijmakers, J A M , Sterk, P J , de Boer, A , Postma, D S , de Jongste, J C , Maitland-van der Zee, A H , Koenderman, L , Koppelman, G H , de Bakker, P I W , Duiverman, E J

in 45/43 / 692/308/575 / Adrenal Cortex Hormones - therapeutic use / Anti-Asthmatic Agents - therapeutic use / Asthma / Asthma - drug therapy / Asthma - genetics / Asthma - physiopathology / Asthma in children / Biomedical and Life Sciences / Biomedicine / Care and treatment / Child / Childhood / Children / Childrens health / Chromosome 17 / Chromosomes, Human, Pair 17 - genetics / Corticosteroids / Drug metabolism / Female / Gene Expression / Genetic aspects / Genetic Association Studies / Genetic diversity / Genetic Loci / Genetic variation / Health aspects / Human Genetics / Humans / Identification and classification / Inhaled medication / Male / Methacholine / Oncology / original-article / Patient outcomes / Pharmacotherapy / Phenotype / Polymorphism, Single Nucleotide / Psychopharmacology / Respiratory function / Single-nucleotide polymorphism / Treatment Failure

2016

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Genetic variation in uncontrolled childhood asthma despite ICS treatment

2016

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Genetic variation in uncontrolled childhood asthma despite ICS treatment

2016

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Journal Article

Genetic variation in uncontrolled childhood asthma despite ICS treatment

Vijverberg, S J H,

Leusink, M,

Onland-Moret, N C,

Raaijmakers, J A M,

Sterk, P J,

de Boer, A,

Postma, D S,

de Jongste, J C,

Maitland-van der Zee, A H,

Koenderman, L,

Koppelman, G H,

de Bakker, P I W,

Duiverman, E J

2016

Overview

Genetic variation may partly explain asthma treatment response heterogeneity. We aimed to identify common and rare genetic variants associated with asthma that was not well controlled despite inhaled corticosteroid (ICS) treatment. Data of 110 children was collected in the Children Asthma Therapy Optimal trial. Associations of genetic variation with measures of lung function (FEV 1 %pred), airway hyperresponsiveness (AHR) to methacholine (Mch PD20) and treatment response outcomes were analyzed using the exome chip. The 17q12-21 locus (containing ORMDL3 and GSMDB) previously associated with childhood asthma was investigated separately. Single-nucleotide polymorphisms (SNPs) in the 17q12-21 locus were found nominally associated with the outcomes. The strongest association in this region was found for rs72821893 in KRT25 with FEV 1 %pred ( P =3.75*10 −5 ), Mch PD20 ( P =0.00095) and Mch PD20-based treatment outcome ( P =0.006). No novel single SNPs or burden tests were significantly associated with the outcomes. The 17q12-21 region was associated with FEV 1 %pred and AHR, and additionally with ICS treatment response.

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Publisher

Nature Publishing Group UK,Nature Publishing Group

Subject

45/43

/ 692/308/575

/ Adrenal Cortex Hormones - therapeutic use

/ Anti-Asthmatic Agents - therapeutic use

/ Asthma

/ Asthma - drug therapy

/ Asthma - genetics