Effects of β-Adrenoceptor and Catechol-O-Methyl-Transferase (COMT) Polymorphism on Postoperative Outcome in Cardiac Surgery Patients

Med Sci Monit Basic Res. 2017 May 19:23:223-233. doi: 10.12659/msmbr.902820.

Abstract

BACKGROUND There is a long-standing debate about the role of beta-adrenoceptor polymorphisms in the cardiovascular system. We wanted to elucidate whether β1-adrenoceptor-polymorphisms affects the postoperative catecholamine consumption and the length of intermediate care unit stay in patients undergoing cardiac surgery, and whether this might be enhanced or attenuated by catechol-O-methyl-transferase (COMT) polymorphism. MATERIAL AND METHODS We included 116 patients (63±1.2 years; 34% females; 81±1 kg) undergoing cardiac surgery. We assessed Arg389Gly and Ser49Gly-β1-adrenoceptor (B1AR) polymorphism together with Val158Met-COMT polymorphism by real-time PCR using fluorescence resonance energy transfer (PCR-FRET). The preoperative risk was assessed by EuroSCORE. In addition, we measured the endogenous preoperative epinephrine and norepinephrine plasma concentrations using an electrochemical HPLC method. RESULTS 84.6% were homozygous for Ser49Ser, 52.1% homozygous for Arg389Arg B1AR, and 32.5% for Val158Val-COMT, while 15.4% showed Ser49Gly B1AR, 38.5% Arg389Gly-B1AR, and 35.6% Val158Met-COMT. We found that the Gly49-variant, the Gly389-variant, and the Val158-COMT-variant were associated with higher postoperative norepinephrine consumption. All patients carrying the Val158-COMT allele exhibited higher preoperative norepinephrine concentrations. Moreover, we found that both β1-adrenoceptor polymorphisms were associated with a longer stay in hospital, which was modulated by the COMT polymorphism. CONCLUSIONS These data show that the β1-adrenoceptor polymorphisms, together with the COMT polymorphism, affect norepinephrine consumption and stay in hospital in a situation of enhanced cardiovascular stress, reflected here by the postoperative period after cardiac surgery. Moreover, we conclude that patients with the Val158-COMT genotype exhibit higher endogenous resting plasma norepinephrine levels.

MeSH terms

  • Aged
  • Alleles
  • Cardiac Surgical Procedures
  • Catechol O-Methyltransferase / genetics*
  • Catechol O-Methyltransferase / metabolism
  • Catecholamines / metabolism
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Germany
  • Humans
  • Length of Stay
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics
  • Receptors, Adrenergic / genetics
  • Receptors, Adrenergic, beta-1 / genetics*
  • Receptors, Adrenergic, beta-1 / metabolism*
  • Thoracic Surgery
  • Treatment Outcome

Substances

  • Catecholamines
  • Receptors, Adrenergic
  • Receptors, Adrenergic, beta-1
  • Catechol O-Methyltransferase