Influence of Beta-1 Adrenergic Receptor Genotype on Cardiovascular Response to Exercise in Healthy Subjects

BACKGROUND: The beta-1 adrenergic receptor (ADRB1) has been shown to play a functional role in cardiomyocyte function and accounts for up to 80% of the cardiac tissue adrenergic receptors with ADRB1 stimulation increasing cardiac rate, contractility and work. Multiple polymorphisms of the ADRB1 have been identified such as the Gly49 polymorphism that includes at least one glycine (Gly) for serine (Ser) at amino acid 49 resulting in either homozygous for Gly (Gly49Gly) or heterozygous for Gly (Gly49Ser) polymorphisms. Heart failure patients with this polymorphism (Gly49) have been shown to have improved cardiac function and decreased mortality risk, but if there is an effect in healthy subjects is less clear. The purpose of this study was to determine the effects of the Gly/Ser polymorphism at position 49 of the ADRB1on the cardiovascular response to exercise in healthy subjects. METHODS: We performed genotyping of the ADRB1 (amino acid 49) and high-intensity, steady-state exercise on 71 healthy subjects (Ser49Ser = 52, Gly49Ser = 19). RESULTS: There were no differences between genotype groups in age, height, weight, body mass index (BMI), or watts achieved (age = 28.9 ± 5.6 years (yrs.), 30.6 ± 6.4yrs., height = 173.6 ± 9.9 cm, 174 ± 7.5 cm, weight = 74.4 ± 13.3 kg, 71.9 ± 13.5 kg, BMI = 24.6 ± 3.5, 23.6 ± 3.3, and watts = 223.8 ± 76.8, 205 ± 49.4, for Ser49Ser and Gly49Ser respectively). Additionally, there were no differences for genotype groups for cardiac output (CO), systolic blood pressure (BP(sys)), or diastolic blood pressure (BP(dias)) at rest, maximal exercise, or in change from rest to maximal exercise. The genotype groups differed significantly in heart rate (HR(max)) at maximal exercise and cardiac index at rest (CI) (HR(max) = 184.2 ± 9.5 bpm, 190.7 ± 10.6 bpm, CI = 0.063 ± 0.014, 0.071 ± 0.013, for Ser49Ser and Gly49Ser respectively). There was a trend towards significance (P = 0.058) for the change in stroke volume from rest to peak exercise (ΔSV) (0.016 ± 0.018 L, 0.0076 ± 0.012 L, for Ser49Ser and Gly49Ser respectively). CONCLUSIONS: These data suggest genetic variations of the ADRB1 may influence cardiovascular responses to exercise in healthy subjects.