2 -ADRENERGIC RECEPTOR AND THE CIRCULATION Niels V. Olsen, MD, - - PowerPoint PPT Presentation

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2 -ADRENERGIC RECEPTOR AND THE CIRCULATION Niels V. Olsen, MD, - - PowerPoint PPT Presentation

Oct 29, 2023 343 likes •621 views

GENETIC VARIATION IN THE 2 -ADRENERGIC RECEPTOR AND THE CIRCULATION Niels V. Olsen, MD, DMSc Department of Biomedicine University of Copenhagen Single nucleotide polymorphism (SNP) Single nucleotide polymorphisms (SNPs) in -adrenergic

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GENETIC VARIATION IN THE β2-ADRENERGIC RECEPTOR AND THE CIRCULATION

Niels V. Olsen, MD, DMSc Department of Biomedicine University of Copenhagen

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Single nucleotide polymorphism (SNP)

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Single nucleotide polymorphisms (SNPs) in β-adrenergic receptors

ADRB2 ADRB1

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How does ADRB2 variation influence circulation in ’normal’ subjects

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The Gly16Arg SNP seems to have an independent effect

  • n haemodymics in humans
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Rokamp et al 2013

Effects of the Gly16Arg SNP in ADRB2 and the ACE I/D polymorphism

  • n resting Q and Q during

submaximal exercise

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Presence of the Gly16 allele in healthy subjects is associated with greater cardiac output and β2-mediated vasodilation

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Dose-dependent effect of the Gly16 allele on cardiac output

Snyder et al 2006

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Hesse et al 2010

The Gly16 allele enhances β2-mediated vasodilatation after baroreflex ablation with Trimethaphan

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Anesth Analg 2016; 122: 1385-93

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Nielsen et al 2014

Gly16 homozygote subjects received 32% more ephedrine than Arg16 homozygotes (p = 0.0068, 95% CI: 8%-63%).

Gly16Arg SNP in ADRB2 and perioperative haemodynamics

N = 564 Caucasians Neurosurgery

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Gly16Arg SNP in ADRB2 and perioperative haemodynamics

Staalsoe et al 2014 N = 168 AAA patients

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Staalsoe et al 2014

Gly16 homozygotes have higher ScO2 perioperatively compared with Arg16 carriers This association seems to rely on the effect of Gly16 on Q

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Staalsoe et al 2014

Effects of the Gly16Arg SNP in ADRB2

  • n relation between Q and age

N = 168 AAA patients

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N = 40 healthy Caucasians During infusion of epinephrine plasma glucose was 1.9 mM higher in the Gly/Gly compared with Arg/Arg homozygotes (p = 0.0001) A genotype specific modulation

  • f epinephrine-induced glycolysis?
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0% 10% 20% 30% 40% 50% 60% Total Normal awareness Impaired awareness

* **

AA GA GG GG GA AA AA GA GG

Prevalence of severe hypoglycemia (%)

ADVANCE ARTICLE

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1 2 3 4 5 6 7

GG GA AA GG GA AA GG GA AA

Total Normal awareness Impaired awareness

** *

Relative Risk of severe hypoglycemia (CI95)

ADVANCE ARTICLE

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How does ADRB2 polymorphism affect the receptor function?

Receptor density Agonist-mediated desensitization Degradation

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ADRB2 genetic variation and cardiovascular health

  • In heart failure, Arg16 increases risk of adverse outcome

(Shin et al 2007, de Groote et al 2005)

  • Survival after acute coronary syndrome better with Gly16

in African-Americans (Cresci et al 2012)

  • No influence on survival in heart failure patients

(Sehnert et al 2008)

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Conclusions

  • 1. Presence of the Gly16 allele is linked with greater

cardiac output and β2-mediated vasodilation

  • 2. Genetic variation in the gene encoding the β2-adrenergic

receptor (ADRB2) has a role in regulation of perioperative haemodynamics in general anaesthesia

  • 3. ADRB2 variation may predict cardiovascular health