OBJECTIVE: To determine whether genetic polymorphisms of the beta2-adrenergic receptor gene affect the relationship between albuterol (INN, salbutamol) plasma concentrations and the forced expiratory volume in 1 second (FEV1) in subjects with moderate asthma. METHODS: Sixteen clinically stable patients with moderate asthma who participated in a pharmacokinetic-pharmacodynamic study of albuterol volunteered to provide a blood sample for determination of beta2-adrenergic receptor genotype. FEV1 and plasma concentrations of albuterol were determined at various times after administration of an oral solution that contained 8 mg albuterol. Patients withheld inhaled beta2-agonist and corticosteroid therapy 12 and 24 hours, respectively, before the study. beta2-Adrenergic receptor genotype was determined by polymerase chain reaction with allele-specific oligonucleotide hybridization. RESULTS: Albuterol-evoked FEV1 was higher and the response was more rapid in Arg16 homozygotes compared with the cohort of carriers of the Gly16 variant: Maximal percentage increase in FEV1 (%deltaFEV1), 18% versus 4.9% (P < .03); area under FEV1 albuterol concentration curve, 194%.mL/ng versus 30%.mL/ng (P < .05); initial slope (dE/dC), 1.43%.mL/ng versus 0.55%.mL/ng (P < .003). CONCLUSIONS: The beta2-adrenergic receptor gene polymorphism is a major determinant of bronchodilator response to albuterol. Future pharmacodynamic studies of beta2-agonists should include determination of 02-adrenergic receptor genotype.
OBJECTIVE: To determine whether genetic polymorphisms of the beta2-adrenergic receptor gene affect the relationship between albuterol (INN, salbutamol) plasma concentrations and the forced expiratory volume in 1 second (FEV1) in subjects with moderate asthma. METHODS: Sixteen clinically stable patients with moderate asthma who participated in a pharmacokinetic-pharmacodynamic study of albuterol volunteered to provide a blood sample for determination of beta2-adrenergic receptor genotype. FEV1 and plasma concentrations of albuterol were determined at various times after administration of an oral solution that contained 8 mg albuterol. Patients withheld inhaled beta2-agonist and corticosteroid therapy 12 and 24 hours, respectively, before the study. beta2-Adrenergic receptor genotype was determined by polymerase chain reaction with allele-specific oligonucleotide hybridization. RESULTS:Albuterol-evoked FEV1 was higher and the response was more rapid in Arg16 homozygotes compared with the cohort of carriers of the Gly16 variant: Maximal percentage increase in FEV1 (%deltaFEV1), 18% versus 4.9% (P < .03); area under FEV1 albuterol concentration curve, 194%.mL/ng versus 30%.mL/ng (P < .05); initial slope (dE/dC), 1.43%.mL/ng versus 0.55%.mL/ng (P < .003). CONCLUSIONS: The beta2-adrenergic receptor gene polymorphism is a major determinant of bronchodilator response to albuterol. Future pharmacodynamic studies of beta2-agonists should include determination of 02-adrenergic receptor genotype.
Authors: Melanie C Matheson; Justine A Ellis; Joan Raven; David P Johns; E Haydn Walters; Michael J Abramson Journal: J Hum Genet Date: 2006-09-01 Impact factor: 3.172
Authors: Victor E Ortega; Gregory A Hawkins; Stephen P Peters; Eugene R Bleecker Journal: Immunol Allergy Clin North Am Date: 2007-11 Impact factor: 3.479