Genotype related differences in β2 adrenergic receptor density and cardiac function

Eric M. Snyder, Minelle L. Hulsebus, Stephen T Turner, Michael Joseph Joyner, Bruce David Johnson

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Introduction: Several common polymorphisms of the β2 adrenergic (ADRB2) have been described including a Glycine (Gly) for arginine (Arg) substitution at amino acid 16. In vivo studies have attributed phenotypic differences in the Arg16Gly polymorphism of the ADRB2 to differences in agonist-mediated desensitization. Some studies, however, have shown differences between genotype groups under non-agonist-mediated conditions suggesting baseline differences in receptor function or in receptor density. We sought to determine whether genetic variation of the ADRB2 influenced ADRB2 density and, consequently, resting cardiovascular function. Methods: We measured ADRB2 density on isolated lymphocytes in 30 healthy subjects (15 homozygous for Arg, Arg16, and 15 homozygous for Gly, Gly 16) matched for age, cardiovascular fitness, BMI, and gender. In addition, we measured cardiac output (Q), heart rate (HR), and stroke volume (SV) after 5 min of quiet rest in these same subjects. Results: Arg16 subjects had lower receptor density (1220 ± 78 vs 1574 ± 110, mean ± SE, P < 0.01) as well as lower resting cardiac output due to a reduced stroke volume, but a higher HR when compared with the Gly 16 subjects (Q = 4.3 ± 0.2 vs 5.0 ± 0.3 L·min-1, SV = 65 ± 6 vs 86 ± 7 mL·beat-1, HR = 70 ± 4 vs 60 ± 3 beats·min-1, for the Arg16 and Gly16 groups, respectively, P < 0.01). In addition, ADRB2 density for all subjects was positively associated with cardiac output (r = 0.428, P = 0.009) and stroke volume (r = 0.407, P = 0.001). Conclusions: These data suggest that the Arg16Gly polymorphism of the ADRB2 influences receptor density, which, in turn, contributes to resting differences in cardiac output and stroke volume.

Original languageEnglish (US)
Pages (from-to)882-886
Number of pages5
JournalMedicine and Science in Sports and Exercise
Volume38
Issue number5
DOIs
StatePublished - May 2006

Fingerprint

Stroke Volume
Adrenergic Receptors
Cardiac Output
Glycine
Genotype
Cardiac Volume
Heart Rate
Arginine
Amino Acid Substitution
Adrenergic Agents
Healthy Volunteers
Lymphocytes

Keywords

  • Adrenergic
  • Cardiac
  • Polymorphism
  • Receptor

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Physical Therapy, Sports Therapy and Rehabilitation
  • Orthopedics and Sports Medicine

Cite this

Genotype related differences in β2 adrenergic receptor density and cardiac function. / Snyder, Eric M.; Hulsebus, Minelle L.; Turner, Stephen T; Joyner, Michael Joseph; Johnson, Bruce David.

In: Medicine and Science in Sports and Exercise, Vol. 38, No. 5, 05.2006, p. 882-886.

Research output: Contribution to journalArticle

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AB - Introduction: Several common polymorphisms of the β2 adrenergic (ADRB2) have been described including a Glycine (Gly) for arginine (Arg) substitution at amino acid 16. In vivo studies have attributed phenotypic differences in the Arg16Gly polymorphism of the ADRB2 to differences in agonist-mediated desensitization. Some studies, however, have shown differences between genotype groups under non-agonist-mediated conditions suggesting baseline differences in receptor function or in receptor density. We sought to determine whether genetic variation of the ADRB2 influenced ADRB2 density and, consequently, resting cardiovascular function. Methods: We measured ADRB2 density on isolated lymphocytes in 30 healthy subjects (15 homozygous for Arg, Arg16, and 15 homozygous for Gly, Gly 16) matched for age, cardiovascular fitness, BMI, and gender. In addition, we measured cardiac output (Q), heart rate (HR), and stroke volume (SV) after 5 min of quiet rest in these same subjects. Results: Arg16 subjects had lower receptor density (1220 ± 78 vs 1574 ± 110, mean ± SE, P < 0.01) as well as lower resting cardiac output due to a reduced stroke volume, but a higher HR when compared with the Gly 16 subjects (Q = 4.3 ± 0.2 vs 5.0 ± 0.3 L·min-1, SV = 65 ± 6 vs 86 ± 7 mL·beat-1, HR = 70 ± 4 vs 60 ± 3 beats·min-1, for the Arg16 and Gly16 groups, respectively, P < 0.01). In addition, ADRB2 density for all subjects was positively associated with cardiac output (r = 0.428, P = 0.009) and stroke volume (r = 0.407, P = 0.001). Conclusions: These data suggest that the Arg16Gly polymorphism of the ADRB2 influences receptor density, which, in turn, contributes to resting differences in cardiac output and stroke volume.

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