Tailored therapy in asthma? ADRB2 genotype in the context of salmeterol therapy

In a recent trial, asthmatic children homozygous for the beta2-adrenergic receptor Arg16 variant (ADRB2 gene, rs1042713 genotype AA) were randomized and treated with either salmeterol (a beta2-adrenergic receptor agonist) or montelukast (a leukotriene receptor antagonist), both combined with fluticasone. Those in the montelukast treatment group displayed significantly better responses in several symptom categories, had fewer school absences, and overall had significantly higher quality of life scores over the 1 year period compared to those treated with salmeterol. [Click here for Further details]

Tailored second line therapy in asthmatic children with the arginine-16 genotype. Lipworth BJ, Basu K, Donald HP, Tavendale R, Macgregor DF, Ogston SA, Palmer CN, Mukhopadhyay S. Clinical Science (2013) 124, (517-519).

This trial was based on previous studies from the same group showing an increased risk of asthma exacerbations in children with daily exposure to beta2-adrenergic receptor agonists who have the ADRB2 Arg16 variant: 

• "Arginine-16 beta2 adrenoceptor genotype predisposes to exacerbations in young asthmatics taking regular salmeterol" Palmer et al, (2006). 
• "Adrenergic beta(2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol" Basu et al, (2009).

These studies suggest that alternative treatments may be more beneficial in children with the Arg16/Arg16 genotype compared to using beta2 adrenergic receptor agonists.

Learn more about Beta-agonist action on ADRB2:

PharmGKB Beta-agonist/Beta-blocker Pathway, Pharmacodynamics

Learn more about the ADRB2 gene:

ADRB2 Very Important Pharmacogene summary