Effect of [beta] sub(2)-adrenergic receptor gene (ADRB2) 3' untranslated region polymorphisms on inhaled corticosteroid/long-acting [beta] sub(2)-adrenergic agonist response

• Published in: Respiratory research 2012-01, Vol.13 (1), p.37-37
• Main Authors: Ambrose, Helen J, Lawrance, Rachael M, Cresswell, Carl J, Goldman, Mitchell, Meyers, Deborah A, Bleecker, Eugene R
• Format: Article
• Language: English
• ISSN: 1465-9921
• DOI: 10.1186/1465-9921-13-37

Background: Evidence suggests that variation in the length of the poly-C repeat in the 3' untranslated region (3'UTR) of the [beta] sub(2)-adrenergic receptor gene (ADRB2) may contribute to interindividual variation in [beta]-agonist response. However, methodology in previous studies limited the assessment of the effect of sequence variation in the context of poly-C repeat length. The objectives of this study were to design a novel genotyping method to fully characterize sequence variation in the ADRB2 3'UTR poly-C repeat in asthma patients treated with inhaled corticosteroid and long-acting [beta] sub(2)-adrenergic agonist (ICS/LABA) combination therapy, and to analyze the effect of the poly-C repeat polymorphism on clinical response. Methods: In 2,250 asthma patients randomized to treatment with budesonide/formoterol or fluticasone/salmeterol in a six-month study (AstraZeneca study code: SD-039-0735), sequence diversity in the ADRB2 poly-C repeat region was determined using a novel sequencing-based genotyping method. The relationship between the poly-C repeat polymorphism and the incidence of severe asthma exacerbations, and changes in pulmonary function and asthma symptoms from baseline to the average during the treatment period, were analyzed. Results: Poly-C repeat genotypes were assigned in 97% (2,192/2,250) of patients. Of the 13 different poly-C repeat alleles identified, six alleles occurred at a frequency of >5% in one or more population in this study. The repeat length of these six common alleles ranged from 10 to 14 nucleotides. Twelve poly-C repeat genotypes were observed at a frequency of >1%. No evidence of an association between poly-C repeat genotype and the incidence of severe asthma exacerbations was observed. Patients' pulmonary function measurements improved and asthma symptoms declined when treated with ICS/LABA combination therapy regardless of poly-C repeat genotype. Conclusions: The extensive sequence diversity present in the poly-C repeat region of the ADRB2 3'UTR did not predict therapeutic response to ICS/LABA therapy.