Effect of genetic variation on healthcare outcomes in children and adults with eczema and asthma

Abstract

Background: Asthma and eczema are common chronic diseases. Filaggrin (FLG), Adrenoreceptor β2 (ADRB2), and the Fc fragment of IgE receptor II (FCER2) gene have been associated with asthma and eczema susceptibility, clinical response to medication and asthma exacerbations. However, it is unclear whether these genotypes contribute to differences in healthcare outcomes such as prescribing and whether these lead to different healthcare costs. Methods: A systematic review was undertaken to identify evidence on pharmacogenetic associations in asthma and to inform which genetic model to use for secondary analysis of BREATHE, a study of gene-environment associations with asthma severity. BREATHE data were collected on 1100 children and young adults with asthma, in Tayside and Fife, Scotland. A collaboration with the Health Informatics Centre, Dundee, enabled BREATHE to be linked to routine healthcare data over 9-years: A&E attendances, hospital admissions, and community prescribing. Data were analysed using generalised linear models with random effects. Public engagement activities were performed to understand parent’s and children’s opinion about personalised medicine in asthma and eczema. Results: An association was found between the presence of FLG mutations and prescribing of emollients (IRR: 2.19, 95% CI: 1.36-3.52), treatment for severe eczema (IRR: 2.18, 95% CI: 1.22-3.91), prescribing of a combination of Long-acting β2-agonists (LABA)/Inhaled Corticosteroid (ICS) (IRR: 3.29, 95% CI: 1.68-6.43), and asthma-related hospitalisations (IRR: 2.37, 95% CI: 1.51-3.71). An association was found between the Arg16Gly polymorphism and the prescribing of Leukotriene Receptor Antagonist (LTRA) (Gly/Gly vs. Arg/Arg − IRR: 2.33, 95% CI: 1.06-5.13), and a combination of LABA/ICS (Gly/Arg vs. Arg/Arg − IRR: 2.80, 95% CI: 1.35-5.81; Gly/Gly vs. Arg/Arg − IRR: 3.15, 95% CI: 1.50-6.63). An association was found between the Glu27Gln polymorphism and the prescribing of LTRA (Gln/Gln vs. Gln/Glu − IRR: 0.53, 95% CI: 0.29-0.98; Gln/Gln vs. Glu/Glu IRR: 0.43, 95% CI: 0.20-0.95) and a combination of LABA/ICS (Gln/Gln vs. Glu/Glu − IRR: 0.47, 95% CI: 0.23-0.98). FCER2 was associated with prescribing of LTRA (TT vs. CC − IRR: 3.85, 95% CI: 1.43-10.34; TC vs. CC IRR: 4.96, 95% CI: 1.77-13.86). Patients with FLG mutations or with Arg/Arg genotype had greater healthcare costs than patients without FLG mutations or with Gly/Arg or Gly/Gly genotype. Conclusion: Genetic variations in FLG, Arg16Gly and FCER2 exert long-term influences on healthcare outcomes. The ability to define genetic subgroups requiring more long-term medication or those not responding to particular medications could help develop targeted management strategies, potentially reducing morbidity and treatment costs.

Date of Award	Jul 2018
Original language	English
Awarding Institution	University of Brighton
Supervisor	S. Mukhopadhyay (Supervisor)