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Int J Sports Med. 2013 Mar;34(3):274-80. doi: 10.1055/s-0032-1316365. Epub 2012 Oct 12.

GNAS A-1121G variant is associated with improved diastolic dysfunction in response to exercise training in heart failure patients.

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Faculty of Sport, Research Centre in Physical Activity, Health and Leisure, University of Porto, Porto, Portugal.


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.

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