191 - Pharmacogenetics of Inhaled Corticosteroids in Obesity related Childhood Asthma

Poster Number: 191
Publication Number: 191.592

Background: Asthma is a multifactorial disease with genetic and environmental risk factors playing a role in pathogenesis and therapeutic response. Worsened disease severity in children with asthma and obesity vs children with asthma and no obesity can be explained by phenotypic characteristics (airway dysanapsis, dyspnea, increased ventilatory needs with obesity) and inflammatory processes (circulating cardiometabolic factors/inflammatory cytokines including adipokines). The inflammatory processes underlying both asthma and obesity can contribute to severity of the disease and poor medication response. Inhaled corticosteroids (ICS) are commonly prescribed asthma medications for the long-term control of persistent asthma, but 25-30% of patients do not respond to ICS. Genetic variations in T, GLCCI1, CRHR1 genes have been previously associated with differences in ICS response. This study aims to investigate whether obesity as an endotype influences pharmacogenetics of ICS response.

Objective: This study aims to investigate whether obesity as an endotype influences pharmacogenetics of ICS response.

Design/Methods: We conducted a candidate gene analysis to examine whether pharmacogenetic associations are stronger when stratifying the Caucasian Childhood Asthma Management Program (CAMP) cohort by obesity status (BMI percentile >95%). We dichotomized the cohort based on obesity status into non-obese (n=176) and obese (n=25) categories and performed genetic association analysis with 2-month change in lung function following ICS for the SNPs rs6456042, rs37972, rs242941, rs1876828, rs9955411, previously associated with ICS response.

Results: In an additive model, we observed a 5.7% increase in Forced expiratory volume in the first second percentage predicted (FEV1PP) for the entire cohort (p=0.003), while the %change (p values) were -6.2% (p=0.26) for obesity status and 6.6% (p=0.001) for non-obese groups respectively. Correspondingly, there were significant pharmacogenomic associations with ICS response in the non-obese group, with a trend in the opposite direction for rs37972 for the obese group.

Conclusion(s): We found a negative correlation of obesity status with change in lung function after ICS treatment. Pharmacogenetic responses to ICS are better classified in children with no obesity, but future studies looking for obese specific loci should be conducted. In our study, although no association remained statistically significant in children with obesity status, our findings provide evidence that obesity as an endotype may influence pharmacogenetics of ICS response.