GNAS A-1121G variant is associated with improved diastolic dysfunction in response to exercise training in heart failure patients.
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.
Faculty of Sport, Research Centre in Physical Activity, Health and Leisure, University of Porto, Porto, Portugal. alberto.jorge.alves@gmail.com
A J
AJ
Alves
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E
Goldhammer
F
F
Ribeiro
N
N
Eynon
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S
Ben-Zaken Cohen
J A
JA
Duarte
J L
JL
Viana
M
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Sagiv
J
J
Oliveira
D000368:Aged; D000704:Analysis of Variance; D002864:Chromogranins; D005080:Exercise Test; D005081:Exercise Therapy; D017079:Exercise Tolerance / Q000235:genetics* / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005819:Genetic Markers; D060005:Genotyping Techniques; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology / Q000534:rehabilitation*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D016896:Treatment Outcome; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000235:genetics* / Q000502:physiology
C547787:ADRB1 protein, human; D002864:Chromogranins; D005819:Genetic Markers; D018342:Receptors, Adrenergic, beta-1; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs