Arg16Gly polymorphism of the beta2-adrenergic receptor is associated with differences in cardiovascular function at rest and during exercise in humans

Abstract

In humans, subjects homozygous for arginine (ArgArg) at codon 16 of the beta2-adrenergic receptor (beta2AR) have been shown to have greater agonist-mediated desensitization than subjects homozygous for glycine (GlyGly). We sought to determine if this substitution differentially influenced cardiovascular function during short duration (9 min) low and high intensity exercise (40 and 75% of peak work). Healthy Caucasian ArgArg (n = 16), GlyGly (n = 31) and ArgGly (n = 17) subjects matched for age, sex and peak oxygen uptake were studied. There were no differences in adrenaline (ADR) at rest or with heavy exercise, but the ArgArg group had lower ADR with light exercise (P = 0.04). Resting heart rate (HR) was higher in ArgArg (P < 0.01), while cardiac output (Q), stroke volume (SV), and mean arterial pressure (MAP) were lower than the other groups (HR = 86+/-2, 78+/-2, 80+/-1 beats min(-1); Q = 5.7+/-0.81, 6.1+/-0.18, 6.7+/-0.22 l min(-1); SV = 68+/-3, 82+/-3, 89+/-4 ml beat(-1); MAP = 92+/-1, 103+/-2, 98+/-1 mmHg-- for ArgArg, ArgGly and GlyGly, respectively, means +/-s.e.m., P < 0.01), however, no differences were observed in systemic vascular resistance (SVR). With low intensity exercise and high intensity exercise the ArgArg group continued to have a lower , SV and MAP compared to the other groups (P < 0.05), with no differences observed in SVR. During recovery, the ArgArg subjects continued to have a lower MAP but there were no differences in HR, , or SVR. These data suggest that subjects homozygous for Arg at codon 16 of the beta2AR have reduced and MAP at rest that persist during exercise with no evidence for differential changes over the course of exercise despite large changes in catecholamines. This may suggest possible genotype-related differences in baseline receptor function or density which causes phenotypic differences at rest that are sustained during short-term exercise.

Figure 1. Cardiovascular function at rest

The black bars represent Arg16 homozygotes, the grey bars represent the heterozygotes, while the patterned bars represent the Gly16 homozygotes. The error bars represent the standard error of the mean. *P < 0.05 when compared to the ArgArg group.

Figure 2. Adrenaline response to light exercise and heavy exercise between genotype groups

The thick grey line represents the Arg16 homozygotes, the dotted line represents the heterozygotes, while the thin black line represents the Gly16 homozygotes. The error bars represent the standard error of the mean. *P < 0.05 ArgArg versus GlyGly.

Figure 3. Cardiovascular function during light and heavy exercise and into recovery according to genotype groups

The thick grey line represents the Arg16 homozygotes, the thin black line represents the Gly16 homozygotes, while the dotted line represents the heterozygous group. The error bars represent the standard error of the mean. *P < 0.05 when compared to the ArgArg group.

Figure 4. Changes in cardiovascular function during heavy exercise according to genotype

The black bars represent Arg16 homozygotes, the grey bars represent the heterozygotes, while the patterned bars represent the Gly16 homozygotes. The error bars represent the standard error of the mean.