β-1 and β-2 adrenoceptor polymorphisms: Functional importance, impact on cardiovascular diseases and drug responses

Pharmacological modulation of β-adrenoceptor function in patients with coexisting chronic obstructive pulmonary disease and chronic heart failure

“…As a consequence, an alteration of bronchodilator response to β-agonists in elderly people has been suggested [109], and also treatment with β-blockers can be more challenging due to desensitization of β-ARs and variable pharmacokinetic responses that occur with age (potentially decreased absorption, metabolism and excretion) [110]. It is clear that it is imperative to individualize therapy for each patient Finally, it must be mentioned that β1-and β2-AR responses to drug treatment exhibit marked interindividual variability [112][113][114]. At present, it seems to be clear that β-AR polymorphisms do not play a role as disease-causing genes, although they might be risk factors, might modify disease, and/or might influence progression of disease.…”

Blood pressure and metabolic phenotypes in relation to the ADRB1 Arg389Gly and ADRA2B I/D polymorphisms in a White population

“…The ADRB1 Arg389Gly polymorphism leads to the substitution of the amino acid arginine by glycine near to the intracellular carboxyl terminal, which is involved in G-protein binding. 1 The ADRA2B insertion/deletion (Ins þ 910Del (I/D)) polymorphism involves the deletion of three glutamic acids from a repeat element in the third intracellular loop of the protein.…”

“…1 The ADRA2B deletion results in a loss of agonistpromoted desensitization. Case-control studies 1 and continuous trait analyses in patients with coronary heart disease 4 demonstrated association of the ADRB1 Arg389Gly polymorphism with hypertension 1 or with systolic 1 or diastolic 1,4 BP. However, none of these studies involved families randomly recruited from a general population.…”

“…Its activation increases BP, stimulates lipolysis, 10 enhances myocardial contractility, 1 and stimulates the release of renin. 1 In transfected Chinese hamster fibroblasts, the ADRB1 Arg389Gly variant affects the receptor's ability to bind the Gs molecule.…”

“…Its activation increases BP, stimulates lipolysis, 10 enhances myocardial contractility, 1 and stimulates the release of renin. 1 In transfected Chinese hamster fibroblasts, the ADRB1 Arg389Gly variant affects the receptor's ability to bind the Gs molecule. 11 The SNP is a 'loss-of-function' polymorphism with the ArgArg homozygotes exhibiting a three-to fourfold higher isoprenaline-stimulated adenylyl cyclase Table 1 Phenotype-genotype associations in population-based analyses The waist-to-hip ratio is the smallest circumference at the waist divided by the largest circumference at the hip level.…”