Role of methylation quantitative trait loci in pediatric asthma in inhaled corticosteroid response
Alberta Wang, MD, MS
BACKGROUND: Asthma is a genetically heritable disease that affects over 8% of children in the United States and is the leading cause of emergency department (ED) visits, hospitalizations, and school absenteeism in children. Up to one-third of childhood asthmatics have a poor response to inhaled corticosteroid (ICS) treatment, the primary therapy for asthma control, and no reliable method exists to predict who will and will not respond to treatment.
GAP: Methylation quantitative trait loci (meQTL) are genetic polymorphisms that influence DNA methylation. The role of meQTL in asthma pharmacogenetics and ICS response in childhood asthma is currently unknown.
HYPOTHESIS: This study hypothesizes that meQTL are important regulators of ICS response in childhood asthma, as measured by a reduction of exacerbations or improvement in lung function, and can predict future exacerbations in pediatric asthmatics on ICS.
METHODS: A candidate gene approach and multivariable linear regression will be used to investigate the association between meQTL and ICS response in two independent cohorts of children with persistent asthma--Childhood Asthma Management Program (CAMP) and Genetic Epidemiology of Asthma in Costa Rica Study (GACRS). The biomarker potential of the identified meQTL will be examined using multivariable logistic regression.
IMPACT: This study will be the first to investigate and develop a novel meQTL prognostic signature for ICS response in pediatric asthmatics. The identification of meQTL associated with ICS response will also serve to inform future translational research on the biological mechanisms of ICS sensitivity and resistance in childhood asthma.