Genetic variation in uncontrolled childhood asthma despite ICS treatment

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

doi:10.1038/tpj.2015.36

Genetic variation in uncontrolled childhood asthma despite ICS treatment

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

Affiliatie UvA

Research output: Contribution to journal › Article › Academic › peer-review

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 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

Original language	English
Pages (from-to)	158-163
Journal	pharmacogenomics journal
Volume	16
Issue number	2
DOIs	https://doi.org/10.1038/tpj.2015.36
Publication status	Published - 2016

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10.1038/tpj.2015.36

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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, A., de Bakker, P. I. W., Koppelman, G. H., & Maitland-van der Zee, A. H. (2016). Genetic variation in uncontrolled childhood asthma despite ICS treatment. pharmacogenomics journal, 16(2), 158-163. https://doi.org/10.1038/tpj.2015.36

@article{35a366687688416abc61b8b0071b9b26,

title = "Genetic variation in uncontrolled childhood asthma despite ICS treatment",

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 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",

author = "M. Leusink and Vijverberg, \{S. J. H.\} and L. Koenderman and Raaijmakers, \{J. A. M.\} and \{de Jongste\}, \{J. C.\} and Sterk, \{P. J.\} and Duiverman, \{E. J.\} and Onland-Moret, \{N. C.\} and Postma, \{D. S.\} and \{de Boer\}, A. and \{de Bakker\}, \{P. I. W.\} and Koppelman, \{G. H.\} and \{Maitland-van der Zee\}, \{A. H.\}",

year = "2016",

doi = "10.1038/tpj.2015.36",

language = "English",

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journal = "pharmacogenomics journal",

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Leusink, M, Vijverberg, SJH, Koenderman, L, Raaijmakers, JAM, de Jongste, JC, Sterk, PJ, Duiverman, EJ, Onland-Moret, NC, Postma, DS, de Boer, A, de Bakker, PIW, Koppelman, GH & Maitland-van der Zee, AH 2016, 'Genetic variation in uncontrolled childhood asthma despite ICS treatment', pharmacogenomics journal, vol. 16, no. 2, pp. 158-163. https://doi.org/10.1038/tpj.2015.36

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T1 - Genetic variation in uncontrolled childhood asthma despite ICS treatment

AU - Leusink, M.

AU - Vijverberg, S. J. H.

AU - Koenderman, L.

AU - Raaijmakers, J. A. M.

AU - de Jongste, J. C.

AU - Sterk, P. J.

AU - Duiverman, E. J.

AU - Onland-Moret, N. C.

AU - Postma, D. S.

AU - de Boer, A.

AU - de Bakker, P. I. W.

AU - Koppelman, G. H.

AU - Maitland-van der Zee, A. H.

PY - 2016

Y1 - 2016

N2 - 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 (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

AB - 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 (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

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DO - 10.1038/tpj.2015.36

M3 - Article

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SN - 1470-269X

VL - 16

SP - 158

EP - 163

JO - pharmacogenomics journal

JF - pharmacogenomics journal

IS - 2

ER -

Genetic variation in uncontrolled childhood asthma despite ICS treatment

Abstract

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