RT info:eu-repo/semantics/doctoralThesis
T1 Genetic factors involved in the response to inhaled corticosteroids in pediatric asthma
A1 Hernández Pacheco, Natalia
K1 Genética humana
K1 Enfermedades pulmonares
AB Inhaled corticosteroids (ICS) are the most commonly prescribed and effective medication to controlasthma symptoms in children and young adults. High variability in the response to this treatment has beendescribed among individuals and populations. These differences have been suggested to be the result of theinteraction of several factors, including an important contribution of the individual’s genetic composition.However, the genetic markers of ICS response identified to date are not able to predict the responsivenessto this medication in clinical practice. This doctoral thesis aimed to identify genetic variants involved in theresponse to asthma treatment with ICS through genomic approaches. A systematic review of the mainfindings of the genomic studies of asthma susceptibility and treatment response published between 2016and 2018 was performed, identifying the genetic markers to be followed up for replication. Two genome-wideassociation studies of asthma exacerbations despite ICS use in admixed and European populations werealso completed, revealing two suggestive novel associations. Additionally, a gene-set enrichment analysis inasthma patients of European descent revealed a potential novel drug for asthma. Genetic associations withthe change in lung function after a short period of ICS therapy were assessed, suggesting a novelassociation of a locus that could be involved in the response to this medication. Finally, the combination oftranscriptomic data from different cell types with genomic information from asthma patients treated with ICSled to the identification of an additional potential novel locus for ICS response. The findings of this doctoralthesis suggest the existence of genetic markers of asthma treatment response specific to certain ancestrygroups and shared among different populations. Moreover, the information about asthma exacerbations wasevidenced as a good predictor of the response to this medication through the validation of previousassociations described for different measures of ICS response.
YR 2021
FD 2021
LK http://riull.ull.es/xmlui/handle/915/25779
UL http://riull.ull.es/xmlui/handle/915/25779
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 04-jun-2024