Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents

Tom Ruffles, Christina J. Jones, Colin Palmer, Steve Turner, Jonathan Grigg, Roger Tavendale, Fiona Hogarth, Petra Rauchhaus, Kristina Pilvinyte, Romanie Hannah, Helen Smith, Roberta Littleford, Brian Lipworth (Lead / Corresponding author), Somnath Mukhopadhyay

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
74 Downloads (Pure)


Introduction: The A allele of rs1042713 (Arg16 amino acid) in the β 2-adrenoreceptor is associated with poor response to long-acting β 2-agonist (LABA) in young people with asthma. Our aim was to assess whether the prescribing of second-line controller with LABA or a leukotriene receptor antagonist according to Arg16Gly genotype would result in improvements in Pediatric Asthma-Related Quality of Life Questionnaire (PAQLQ).

Methods: We performed a pragmatic randomised controlled trial (RCT) via a primary care clinical research network covering England and Scotland. We enrolled participants aged 12–18 years with asthma taking inhaled corticosteroids. 241 participants (mean±SD age 14.7±1.91 years) were randomised (1:1) to receive personalised care (genotype directed prescribing) or standard guideline care. Following a 4-week run-in participants were followed for 12 months. The primary outcome measure was change in PAQLQ. Asthma control, asthma exacerbation frequency and healthcare utilisation were secondary outcomes.

Results: Genotype-directed prescribing resulted in an improvement in PAQLQ compared to standard care (0.16, 95% CI 0.00–0.31; p=0.049), although this improvement was below the pre-determined clinical threshold of 0.25. The AA genotype was associated with a larger improvement in PAQLQ with personalised versus standard care (0.42, 95% CI 0.02–0.81; p=0.041).

Conclusion: This is the first RCT demonstrating that genotype-driven asthma prescribing is associated with a significant improvement in a clinical outcome compared to standard care. Adolescents with the AA homozygous genotype benefited most. The potential role of such β 2-adrenoceptor genotype directed therapy in younger and more severe childhood asthma warrants further exploration.

Original languageEnglish
Article number2004107
JournalEuropean Respiratory Journal
Issue number2
Early online date21 Jan 2021
Publication statusPublished - 1 Aug 2021


  • genotype
  • beta-2 gene polymorphysms
  • paediatric asthma
  • asthma clinical trials
  • Asthma Quality of Life

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


Dive into the research topics of 'Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents'. Together they form a unique fingerprint.

Cite this