Genetic variation in uncontrolled childhood asthma despite ICS treatment
Leusink, M.; Vijverberg, S.J.H.; Koenderman, L.; Raaijmakers, J.A.M.; de Jongste, J.C.; Sterk, P.J.; Duiverman, E.J.; Onland-Moret, N.C.; Postma, D.S.; de Boer, Anthonius; de Bakker, P.I.W.; Koppelman, G.H.; Maitland-van der Zee, A.H.
(2016) The Pharmacogenomics Journal, volume 16, pp.
(Article)
Abstract
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
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of lung function (FEV1%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 FEV1%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 FEV1%pred and AHR, and additionally with ICS treatment response.The Pharmacogenomics Journal advance online publication, 12 May 2015; doi:10.1038/tpj.2015.36.
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Keywords: asthma, child, corticosteroid therapy, exome, forced expiratory volume, genetic variability, human, lung function, mean corpuscular hemoglobin, pharmacogenomics, respiratory tract allergy, single nucleotide polymorphism, therapy, treatment outcome, treatment response, methacholine, Taverne
ISSN: 1470-269X
Publisher: Nature Publishing Group
(Peer reviewed)
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