Genetic variation in uncontrolled childhood asthma despite ICS treatment.

Authors :: Leusink M
Vijverberg SJ
Koenderman L
Raaijmakers JA
de Jongste JC
Sterk PJ
Duiverman EJ
Onland-Moret NC
Postma DS
de Boer A
de Bakker PI
Koppelman GH
Maitland-van der Zee AH
Source :: The pharmacogenomics journal [Pharmacogenomics J] 2016 Apr; Vol. 16 (2), pp. 158-63. Date of Electronic Publication: 2015 May 12.
Publication Year :: 2016
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.