Bronchodilator Response in Relation to β2-Adrenoceptor Haplotype in Patients with Asthma

Abstract

Genetic variation of the ADRB2 does not influence the immediate response to inhaled beta2-agonist. The confounding effect of tolerance resulting from regular beta2-agonist use must be controlled when assessing the pharmacogenetic influences on clinical outcomes with beta2-agonists.

Pharmacogenetics of the β2-Adrenergic Receptor Gene

“…Taylor and co-workers reported that the Drysdale haplotypes were not associated with albuterolinduced FEV1 reversibility in 176 patients selected based on a physician's diagnosis of asthma, not airflow reversibility. 60 Similiar findings were also observed by Hawkins 35 . In contrast, Drysdale and coworkers selected patients based on a spirometric diagnosis of asthma selection criteria that may explain some of the inconsistent findings of these haplotype-based studies.…”

“…56 Several other smaller studies have observed similar effects of Arg 16 Gly genotypes on response to acute SABA therapy with the notable exception of a study by Taylor and co-workers. 47,[58][59][60][61][62][63] Taylor and co-workers selected 176 patients based solely on a physician's diagnosis of asthma and found no relationship between Gly 16 Arg genotypes or ADRβ2 haplotypes and responsiveness to a single dose of albuterol. 60 In the Genetics of Asthma in Latino Americans (GALA) study, Choudhry et al investigated the pharmacogenetic relationship of Gly 16 Arg genotypes with albuterol-induced FEV1 reversibility in two ethnic groups (365 Puerto Rican asthmatics and 294 Mexican-Americans) through family-based and cross-sectional analyses.…”

“…47,[58][59][60][61][62][63] Taylor and co-workers selected 176 patients based solely on a physician's diagnosis of asthma and found no relationship between Gly 16 Arg genotypes or ADRβ2 haplotypes and responsiveness to a single dose of albuterol. 60 In the Genetics of Asthma in Latino Americans (GALA) study, Choudhry et al investigated the pharmacogenetic relationship of Gly 16 Arg genotypes with albuterol-induced FEV1 reversibility in two ethnic groups (365 Puerto Rican asthmatics and 294 Mexican-Americans) through family-based and cross-sectional analyses. 59 In Puerto Ricans, the number of Arg 16 alleles was associated with increasing FEV1 reversibility and showed an additive effect that was more pronounced among those with a baseline FEV1 less than 80% predicted.…”

No Correlation between Beta2-Adrenergic Receptor Polymorphisms and the Severity and Clinical Control of Geriatric Asthma and COPD

“…Additionally, the COPD population, including geriatric patients, may be susceptible to such predilection based upon recent studies [25]. Alternatively, a number of studies refute such associations [3,[26][27][28]. Given the discrepancy in management required if ADRB2 polymorphisms are implicated, our study uniquely studied the clinical effect of ADRB2 polymorphisms in the most progressive population of obstructive lung disease, geriatrics.…”

“…Finally, we did not examine specific treatment regimens in the recruited patients. The relationship between ADRB2 polymorphism and different treatment regimens has been well studied during the last decade with mixed results [3][4][5][6]10,[24][25][26][27][28]. As such, there has been no major paradigm shift in treatment of asthma or COPD with respect to varying ADRB2 polymorphisms.…”