GNAS A-1121G Variant is Associated with Improved Diastolic Dysfunction in Response to Exercise Training in Heart Failure Patients

• Autor(a) principal: Alves, A.
• Data de Publicação: 2012
• Outros Autores: Goldhammer, E., Ribeiro, F., Eynon, N., Ben-Zaken Cohen, S., Duarte, J., Viana, J., Sagiv, M., Oliveira, J.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.24/1779
• topic: Aged; Analysis of Variance; Chromogranins; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; GTP-Binding Protein alpha Subunits, Gs; Genetic Markers; Genotyping Techniques; Heart Failure; Homozygote; Humans; Male; Middle Aged; Receptors, Adrenergic, beta-1; Treatment Outcome; Ultrasonography; Ventricular Function, Left; Exercise Therapy; Polymorphism, Single Nucleotide

β1-adrenergic receptors (ADRB1) and Gαs proteins (GNAS) play important roles in the regulation of cardiac function. The present study sought to investigate whether ADRB1 Arg389Gly (rs1801253), GNAS -1211 G/A (rs6123837) and GNAS 2291 C/T (rs6026584) variants are associated with left ventricular function and exercise tolerance in heart failure patients. 61 heart failure patients completed a 6-month exercise-training programme. Left ventricular ejection fraction (LVEF), mitral inflow velocities (deceleration time, and E/A ratio) and exercise tolerance (METs) were assessed at baseline and following exercise training. There were no associations between the studied variants and LVEF or E/A ratio measured at baseline and after exercise training. Deceleration time of early mitral flow was higher at baseline in GNAS -1211G allele carriers compared with -1211A allele homozygotes (P<0.05). Exercise training attenuated deceleration time in -1211G allele carriers (P<0.05) but not in -1211A allele homozygotes. Moreover, ADRB1 389Gly homozygotes had a greater training-induced increase in exercise tolerance than 389Arg homozygotes (P=0.04). This study shows that the functional GNAS -1121 G/A polymorphism is associated with diastolic function at baseline and in response to exercise training in heart failure patients. Furthermore, our data suggest that ADRB1 Arg389Gly polymorphism may influence exercise tolerance.