Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression.

McGraw, Dennis W.; Forbes, Susan L.; Kramer, Lisa A.; Liggett, Stephen B.

doi:10.1172/jci4862

Cited by 260 publications

(215 citation statements)

References 26 publications

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“…For the 164Ile variant of the Thr164Ile polymorphism located in the fourth transmembrane domain, considerably lower affinities for isoproterenol, epinephrine and norepinephrine associated with decreased basal and agonist-stimulated adenylyl cyclase activity have been documented (Green et al 1993). Finally, carriers of the -19Cys allele in the 5′ cistron have been reported to express significantly more β2AR (McGraw et al 1998).…”

Section: Genetic Variants In β-Adrenoceptor Genesmentioning

confidence: 97%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

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Section: Genetic Variants In β-Adrenoceptor Genesmentioning

confidence: 97%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

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“…Interestingly, levels of the mRNA transcripts between genotypes were similar indicating that Arg 19(BUP) Cys only regulates receptor translation, not transcription. 41 Drysdale and co-workers investigated the interaction of multiple ADRβ2 polymorphisms on transcription and translation after sequencing the gene in a subset of Caucasians, AfricanAmericans, Asians, and Hispanics. 38 38 The effect of the Thr 164 Ile polymorphism on β2-adrenergic receptor binding affinity and coupling to Gs has been studied in CHW-1102 cells.…”

Section: Adrβ2 Pharmacogenetics At the Molecular Levelmentioning

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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“…6 The importance of the ADRB system in cardiovascular physiology has been explored on multiple levels and led to the discovery of multiple polymorphic variants in this system ( Figure 1). 14,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] ADRB1 polymorphisms Twenty-three polymorphisms of ADRB1 have been described and 13 of these predict amino-acid changes in the ADRB1 protein. 14,40 As ADRB1 does not have a recognized role in the pathogenesis of asthma, the majority of genetic association studies have focused on cardiovascular phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics of the human beta-adrenergic receptors

Taylor

2006

Pharmacogenomics J

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The beta-adrenergic receptors (ADRBs) are cell surface receptors that play central roles in the sympathetic nervous system. Pharmacological targeting of two of these receptors, ADRB1 and ADRB2, represents a widely used therapeutic approach for common and important diseases including asthma, hypertension and heart failure. Genetic variation in both ADRB1 and ADRB2 has been linked to both in vitro and clinical disease phenotypes. More recently, interest has shifted to studies that explore potential interaction between variation in ADRBs and medications directed at these important receptors. This paper reviews the current state of knowledge and understanding of ADRB genetic variation and explores the likely direction of future studies in this area.

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Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression.

Cited by 260 publications

References 26 publications

Genetics of arterial hypertension and hypotension

Genetics of arterial hypertension and hypotension

Pharmacogenetics of the β2-Adrenergic Receptor Gene

Pharmacogenetics of the human beta-adrenergic receptors

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