Homozygous status for the Arg16 variant is associated with increased prescribing of controller asthma medication and increased asthma-related prescribing cost

Objectives: Asthma is a chronic respiratory disease, characterised by relapse and remission of symptoms. The Arg16 variant of the ADRB2 gene has been associated with diminished clinical responsiveness to β2‐agonists, and increased risk of asthma exacerbations. The association between this variant and asthma‐related prescribing is unclear. Our hypothesis is that the Arg16 allele is associated with long‐term increased use of prescribed asthma medication.

Method: A secondary analysis of BREATHE, a study of gene‐environment associations with asthma severity, was undertaken. BREATHE data were collected on participants with asthma, aged 3‐22 years, between 2003 and 2005, in Tayside and Fife, Scotland. Through collaboration with the Health Informatics Centre in Dundee, BREATHE was linked to several databases: Accident & Emergency, community prescribing and Scottish Morbidity Records (hospital admissions). This linkage allows exploration of associations between genetic variation and prescribing. Data between 2005 and 2013 were analysed using random effects generalised linear models.

Results: The analysis was performed on 1009 individuals. Over the 9‐year period, a significant association was found between individuals homozygous for the Arg16 variant and the prescribing of prednisolone (Gly/Arg vs Arg/Arg—Incidence Rate Ratio (IRR): 1.54, 95% CI: 1.06‐2.25; Gly/Gly vs Arg/Arg—IRR: 1.64, 95% CI: 1.12‐2.42). A significant association was also found between the Arg16 variant and prescribing of anti‐leukotriene antagonists (Gly/Gly vs Arg/Arg—IRR: 2.33, 95% CI: 1.06‐5.13) and a combination of long‐acting β2‐agonist and corticosteroids (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). Over the 9‐year period, children and adults with the Arg/Arg genotype cost more £250 to the NHS than children and adults with the Gly/Gly or Gly/Arg genotype.

Conclusions: Homozygous individuals with the Arg/Arg variant are associated with long‐term increased prescribing of asthma medication. Defining subgroups of individuals requiring more medication could help develop targeted management strategies.