Asthma: Effect of genotype on Response to Therapy in the Emergency Department

OBJECTIVE: We examined the effect of two β2-adrenoreceptor (β2AR) polymorphisms (A46G and C79G) in asthmatics presenting to the Emergency Department (ED) in relation to their response to standard therapy measured by change in Forced Expiratory Volume at one second (FEV1). Our hypothesis was that the polymorphisms in the β2AR gene would predict clinical response to therapy with 46G and 79C displaying decreased response to inhaled therapy. METHODS: This was a pilot feasibility study of a convenience sample of patients seen in the ED for acute exacerbation of asthma. Baseline data collected included: age, gender, ethnicity, vital signs, baseline FEV1, body mass index (BMI), smoking history and medications taken prior to arrival to the ED. Patients received standard ED care and FEV1 was measured after each treatment. Blood was taken and genotyped. RESULTS: Fifty-three patients were enrolled over a three-month period. Using mean improvement in FEV1 from baseline to the first treatment as the primary outcome of interest, we performed multivariable linear regression analyses, with the FEV1 change as the dependent variable. When modeled as an ordinal covariate representing the number of G alleles present, there was a significant positive trend for the C79G locus (p=0.035). Those who were GG homozygotes had a 0.284 L/min improvement in FEV1 (31%) after their initial albuterol treatment compared to 0.123 L/min (12%) in those who were CC homozygotes. This represents a 2.5 times relative difference and a 19% actual difference. Genotypes at the A46G locus were not associated with FEV1 change. CONCLUSION: In this pilot study of ED patients with acute asthma exacerbation, there was a significant effect of genotype on response to therapy.