Common polymorphisms of β1-adrenoceptor: identification and rapid screening assay

Interacción entre los polimorfismos del receptor ß1 y ß2 adrenérgico como predictor de riesgo de insuficiencia cardiaca crónica

“…El cambio del nucleótido A145G genera la sustitución del aminoácido serina a glicina en el residuo 49 (Ser49Gly), afectando la internalización del receptor dependiente de agonista 3,[5][6][7] . Por otra parte, el cambio G1165C que sustituye glicina por arginina en el residuo 389 (Gly389Arg) se ha asociado a un mayor acoplamiento del receptor a la adenilato ciclasa 4,[6][7][8] . La frecuencia genotípica del ß 1 -RA Arg389Gly depende del grupo étnico 9 y no regula la frecuencia cardiaca basal en sujetos sanos [9][10][11] .…”

Pharmacogenetics of the human beta-adrenergic receptors

“…22,25,69 One study did report Gly49 as a risk factor for idiopathic dilated cardiomyopathy, but the modest population size studied (37 cases and 40 controls) and difference in allele frequency as compared to other studies limit a firm conclusion that Gly49 carriers are at elevated risk. 21,42 This polymorphism, however, may have a role in progression of heart failure as the Ser49 variant was associated with a reduced 5-year survival (risk ratio 2.34; P ¼ 0.003). The other major ADRB1 polymorphism, Arg389-Gly, is not a clear risk factor for heart failure.…”

“…Other known ADRB1 missense polymorphisms are Ser49Gly, Ala59Ser, Arg318Ser, Lys324Arg, Ala343Thr, Glu352Asp, Arg399Cys, Arg400Leu, His402Arg, Thr404Ala, Pro418Ala and Asp460Glu. 14,42,43 The Ser49Gly and Ala59-Ser polymorphisms are located in the extracellular amino terminus and are thought to affect ligand binding. Variants in the intracellular carboxy terminus (Arg389Gly, Arg399Cys, Arg400Leu, His402Arg, Thr404Ala, Pro418Ala, Asp460Glu) could modulate G s protein coupling as is hypothesized for the Arg389Gly variant.…”

Beta blocker specificity: a building block toward personalized medicine

“…New studies reported in this issue of the JCI by Swirski et al (3) demonstrate that a monocyte subset that expresses high levels of a marker antigen, Ly-6C, dominates hypercholesterolemia-associated monocytosis and gives rise to macrophages in atheromata. Also in this issue, Tacke et al (4) report that monocyte subsets differentially employ the chemokine receptors C-C motif chemokine receptor 2 (CCR2), CCR5, and C-X 3 -C motif chemokine receptor 1 (CX3CR1, also known as the fractalkine receptor) to enter atherosclerotic plaques. They also exploited an mAb, Gr-1, directed against Ly-6 family antigens to distinguish monocyte subsets and used CD11c, a β2 integrin expressed by myeloid DCs and selected tisNonstandard abbreviations used: CCR2, C-C motif chemokine receptor 2; CX3CR1, C-X3-C motif chemokine receptor 1.…”