Impact of genetic polymorphisms of the β -adrenergic receptor on albuterol bronchodilator pharmacodynamics

Lima, John J.; Thomason, Donald B.; Mohamed, Mohamad Haniki Nik; Еберле, Л. В.; Self, Timothy H.; Johnson, Julie A.

doi:10.1016/s0009-9236(99)70071-8

Cited by 249 publications

(165 citation statements)

References 20 publications

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“…However, more recent in vivo work in humans has shown the Arg16Gln27 haplotype is the form of the receptor that is associated with agonist-promoted desensitization (Dishy et al 2001). Genetic studies of these polymorphisms have found them to be associated with asthma severity Weir et al 1998), bronchial hyperreactivity (BHR) Ramsay et al 1999), bronchodilator (BD) response (D'Amato et al 1998;Lima et al 1999;Martinez et al 1997;Ulbrecht et al 2000) and lung function (Summerhill et al 2000).…”

Section: Introductionmentioning

confidence: 99%

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

et al. 2006

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The b 2 -adrenergic receptor (b 2 AR) is a transmembrane protein expressed by airway smooth muscle cells. In vitro studies have shown that polymorphisms at amino acid positions 16 and 27 alter receptor function. The aim of this study was to examine the associations between the b 2 AR polymorphisms and risks of asthma, chronic obstructive pulmonary disease (COPD) and respiratory symptoms in a sample of adults. Participants were part of a cross-sectional populationbased study of risk factors for respiratory disease. A total of 1,090 Caucasian participants completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of gas transfer. Genotyping for b 2 AR polymorphisms at positions 16 and 27 was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. Haplotype frequencies for the two polymorphisms were estimated using the E-M algorithm. We found the Arg16 homozygotes had an increased risk of COPD (OR 5.13; 95% CI 1

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Section: Introductionmentioning

confidence: 99%

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

et al. 2006

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“…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.…”

Section: Adrβ2 Pharmacogenetics Asthma Susceptibility and Responsivmentioning

confidence: 99%

Pharmacogenetics of the β2-Adrenergic Receptor Gene

Ortega

Hawkins

Peters

et al. 2007

Immunology and Allergy Clinics of North America

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Asthma is a complex genetic disease with multiple genetic and environmental determinants contributing to the observed variability in response to common anti-asthma therapies. Asthma pharmacogenetic research has focused on multiple candidate genes including the β2-adrenergic receptor gene (ADRβ2) and its effect on individual responses to beta agonist therapy. At present, knowledge about the effects of ADRβ2 variation on therapeutic responses is evolving and should not alter current Asthma Guideline approaches consisting of the use of short acting beta agonists for as-needed symptom based therapy and the use of a regular long-acting beta agonist in combination with inhaled corticosteroid therapy for optimal control of asthma symptoms in those asthmatics who are not controlled on inhaled corticosteroid alone. This approach is based upon studies showing a consistent pharmacogenetic response to regular use of short acting beta agonists (SABA) and less consistent findings in studies evaluating long acting beta agonist (LABA). While emerging pharmacogenetic studies are provocative and should lead to functional approaches, conflicting data with responses to LABA therapy may be caused by factors that include small sample sizes of study populations and differences in experimental design that may limit the conclusions that may be drawn from these clinical trials at the present time.

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“…For instance, the Gly16 variant is associated with more severe asthma 31 and decreased response to an ␤ 2 -AR agonist. 32 Conflicting data exist on the effect of ␤ 2 -AR polymorphisms on blood pressure in the general population. 28,30,33 Nevertheless, healthy whites with Gly16 and Glu27 variants present higher blood pressure.…”

Section: Association Of ␤ 2 -Ar Polymorphisms With Potsmentioning

confidence: 99%

β2-Adrenoceptor Genotype and Function Affect Hemodynamic Profile Heterogeneity in Postural Tachycardia Syndrome

et al. 2006

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Abstract-Previous studies suggest that the ␤2-adrenoceptor functions abnormally in patients with postural tachycardia syndrome (POTS) and may contribute to their altered hemodynamic profile. To test the hypothesis that the ␤2-adrenoceptor response is decreased in POTS, we studied: (1) the arterial vasodilation response to the ␤ agonist, isoproterenol, and (2) the distribution of common polymorphisms (codons 16 and 27) of the gene coding the receptor (␤ 2 -AR) in a large population with POTS. We measured plasma catecholamines and monitored hemodynamics and changes in forearm and leg blood flow to incremental doses of intraarterial isoproterenol in 9 patients with POTS compared with 8 healthy subjects. For polymorphism assessment we collected DNA from 57 patients with POTS and compared with 67 age-sex matched healthy subjects. Circulating catecholamines were significantly higher in POTS subjects compared with controls. Intrabrachial and intrafemoral isoproterenol infusion elicited a dose-dependent increase in blood flow. In healthy subjects, blood flow increased (meanϮSEM) 400Ϯ70% in the forearm and 170Ϯ40% in the leg, but only 280Ϯ60% in forearms and 120Ϯ20% in legs of patients with POTS (ANOVA for both PϽ0.001).The genotype and allele distributions for codons 16 and 27 ␤ 2 -AR variants were not different in the 2 groups. However, the blood pressure and plasma norepinephrine levels diverged in patients according to their genotype. Patients with Gly16Gly and patients with Glu27Glu had lower plasma catecholamines and higher supine and upright blood pressure, compared with other genotypes. Therefore, both decreased ␤2-adrenoceptor-related vasodilation and ␤ 2 -AR polymorphisms may contribute to the hemodynamic diversity of patients with POTS.

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Impact of genetic polymorphisms of the β -adrenergic receptor on albuterol bronchodilator pharmacodynamics

Abstract: 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.

Cited by 249 publications

References 20 publications

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

β2-adrenergic receptor polymorphisms are associated with asthma and COPD in adults

Pharmacogenetics of the β2-Adrenergic Receptor Gene

β2-Adrenoceptor Genotype and Function Affect Hemodynamic Profile Heterogeneity in Postural Tachycardia Syndrome

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